17-43051062-C-T

Variant summary

Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong

The NM_007294.4(BRCA1):​c.5332+1G>A variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.000000684 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★★★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BRCA1
NM_007294.4 splice_donor, intron

Scores

4
2
1
Splicing: ADA: 1.000
2

Clinical Significance

Pathogenic reviewed by expert panel P:13

Conservation

PhyloP100: 4.23

Publications

25 publications found
Variant links:
Genes affected
BRCA1 (HGNC:1100): (BRCA1 DNA repair associated) This gene encodes a 190 kD nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The BRCA1 gene contains 22 exons spanning about 110 kb of DNA. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2020]
BRCA1 Gene-Disease associations (from GenCC):
  • breast-ovarian cancer, familial, susceptibility to, 1
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
  • Fanconi anemia, complementation group S
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
  • pancreatic cancer, susceptibility to, 4
    Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
  • hereditary breast ovarian cancer syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Fanconi anemia
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 18 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-43051062-C-T is Pathogenic according to our data. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-43051062-C-T is described in CliVar as Pathogenic. Clinvar id is 55527.Status of the report is reviewed_by_expert_panel, 3 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRCA1NM_007294.4 linkc.5332+1G>A splice_donor_variant, intron_variant Intron 20 of 22 ENST00000357654.9 NP_009225.1 P38398-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRCA1ENST00000357654.9 linkc.5332+1G>A splice_donor_variant, intron_variant Intron 20 of 22 1 NM_007294.4 ENSP00000350283.3 P38398-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251352
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461614
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727134
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33474
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39698
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111768
Other (OTH)
AF:
0.00
AC:
0
AN:
60388
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000236
Hom.:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:13
Revision: reviewed by expert panel
LINK: link

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 1 Pathogenic:5
Oct 02, 2015
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jun 21, 1999
Breast Cancer Information Core (BIC) (BRCA1)
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

Jun 26, 2023
Baylor Genetics
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
University of Science and Technology Houari Boumediene, Laboratory of Molecular and Cellular Biology (LBCM)
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Apr 03, 2016
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Significance:Pathogenic
Review Status:reviewed by expert panel
Collection Method:curation

Allele-specific assay on patient-derived mRNA demonstrated that the variant allele produces only predicted non-functional transcripts. Variant allele produces r.5278_5332del transcript (encoding predicted non-functional protein). -

not provided Pathogenic:3
-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

Oct 03, 2016
Quest Diagnostics Nichols Institute San Juan Capistrano
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

Hereditary breast ovarian cancer syndrome Pathogenic:3
Nov 16, 2021
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jul 26, 2022
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Variant summary: BRCA1 c.5332+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5 splicing donor site. Experimental evidence supports these predictions demonstrating that this variant affects mRNA splicing, leading to skipping of exon 20 (Colombo_2013). The variant allele was found at a frequency of 4e-06 in 251352 control chromosomes (gnomAD). c.5332+1G>A has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (e.g. Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. Experimental evidence evaluating an impact on protein function through employment of a cell-survival assay in a population of edited haploid HAP1 cells as a measure of functional HDR pathway, determined the variant to be non-functional (Findlay_2018). Seven ClinVar submitters including an expert panel (ENIGMA) (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. -

Sep 04, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This sequence change affects a donor splice site in intron 20 of the BRCA1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or altered protein product. This variant is present in population databases (rs80358041, gnomAD 0.006%). Disruption of this splice site has been observed in individual(s) with breast and/or ovarian cancer (PMID: 11084537, 16324400, 19629752, 27083178). This variant is also known as c.5451+1G>A. ClinVar contains an entry for this variant (Variation ID: 55527). Studies have shown that disruption of this splice site results in skipping of exon 20 (also known as exon 21), and produces a non-functional protein and/or introduces a premature termination codon (PMID: 23451180, 24667779; internal data). For these reasons, this variant has been classified as Pathogenic. -

Hereditary cancer-predisposing syndrome Pathogenic:2
Apr 16, 2025
Ambry Genetics
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.5332+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 19 of the BRCA1 gene. This mutation was found to be de novo in a female diagnosed with bilateral breast cancers at ages 38 and 43 (Edwards E et al. Fam. Cancer. 2009; 8(4):479-82) and has also been reported in a Chinese female with ovarian cancer (Hasmad HN et al. Gynecol. Oncol. 2015 Nov) and in an Algerian female diagnosed with triple negative breast cancer at age 34 (Henouda S et al. Dis. Markers 2016; Epub 2016 Feb 22). RNA splicing assays have shown this alteration to cause coding exon 19 (exon 21 in literature) skipping (Ambry internal data; Colombo M et al. PLoS ONE. 2013; 8(2): e57173; Steffensen AY et al. Eur. J. Hum. Genet. 2014 Dec;22:1362-8). One functional study found that this nucleotide substitution is deleterious in a high throughput genome editing haploid cell survival assay (Findlay GM et al. Nature 2018 10;562(7726):217-222). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. -

Sep 27, 2022
Color Diagnostics, LLC DBA Color Health
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant causes a G to A nucleotide substitution at the +1 position of intron 20 of the BRCA1 gene. RNA studies have reported that this variant causes the out-of-frame skipping of exon 20 resulting in premature termination (PMID: 19629752, 24667779) and a functional study has reported that this variant impacts BRCA1 function in a haploid cell proliferation assay (PMID: 30209399). This variant has been reported in at least five individuals affected with breast or ovarian cancer (PMID: 19629752, 26541979, 26997744, 27083178, 28993434, 30715675, 33471991, 35464868; Leiden Open Variation Database DB-ID BRCA1_000567). This variant has been identified in 1/251352 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.40
CADD
Pathogenic
32
DANN
Uncertain
0.99
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.93
FATHMM_MKL
Uncertain
0.95
D
PhyloP100
4.2
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.9
Mutation Taster
=0/100
disease causing (ClinVar)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.93
Splicevardb
3.0
SpliceAI score (max)
0.99
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.99
Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs80358041; hg19: chr17-41203079; API