rs81002799
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_000059.4(BRCA2):c.426-17G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,449,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
BRCA2
NM_000059.4 splice_polypyrimidine_tract, intron
NM_000059.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0530
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 Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 13-32326084-G-A is Benign according to our data. Variant chr13-32326084-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 51620.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRCA2 | NM_000059.4 | c.426-17G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000380152.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.426-17G>A | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_000059.4 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
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33
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249586Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134950
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GnomAD4 exome AF: 0.00000138 AC: 2AN: 1449462Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 721320
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GnomAD4 genome ? Cov.: 33
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33
ClinVar
Significance: Likely benign
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Breast-ovarian cancer, familial, susceptibility to, 2 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Breast Cancer Information Core (BIC) (BRCA2) | Jul 10, 1998 | - - |
Hereditary breast ovarian cancer syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 19, 2017 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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