rs545321666
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS1
The NM_000059.4(BRCA2):c.-59_-57del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000709 in 152,332 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.00071 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
BRCA2
NM_000059.4 5_prime_UTR
NM_000059.4 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0270
Genes affected
BRCA2 (HGNC:1101): (BRCA2 DNA repair associated) Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer. Both BRCA1 and BRCA2 are involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair. The largest exon in both genes is exon 11, which harbors the most important and frequent mutations in breast cancer patients. The BRCA2 gene was found on chromosome 13q12.3 in human. The BRCA2 protein contains several copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to the RAD51 recombinase which functions in DNA repair. BRCA2 is considered a tumor suppressor gene, as tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele. [provided by RefSeq, May 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP6
Variant 13-32315645-AAAG-A is Benign according to our data. Variant chr13-32315645-AAAG-A is described in ClinVar as [Benign]. Clinvar id is 264878.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32315645-AAAG-A is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000709 (108/152332) while in subpopulation SAS AF= 0.0217 (105/4832). AF 95% confidence interval is 0.0184. There are 0 homozygotes in gnomad4. There are 81 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BRCA2 | NM_000059.4 | c.-59_-57del | 5_prime_UTR_variant | 1/27 | ENST00000380152.8 | NP_000050.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.-59_-57del | 5_prime_UTR_variant | 1/27 | 5 | NM_000059.4 | ENSP00000369497 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000696 AC: 106AN: 152214Hom.: 0 Cov.: 33
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 112Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 76
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GnomAD4 genome AF: 0.000709 AC: 108AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.00109 AC XY: 81AN XY: 74482
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ClinVar
Significance: Benign
Submissions summary: Uncertain:1Benign:4
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Hereditary breast ovarian cancer syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 31, 2018 | - - |
Breast-ovarian cancer, familial, susceptibility to, 2 Benign:1
Benign, reviewed by expert panel | curation | Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) | Sep 28, 2016 | Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.0307 (South Asian), derived from 1000 genomes (2013-05-02). - |
Fanconi anemia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at