ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.10013C>A (p.Ser3338Ter)

dbSNP: rs1593202166
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001465636 SCV001669626 likely benign Hereditary breast ovarian cancer syndrome 2020-08-05 criteria provided, single submitter clinical testing
Genetics and Molecular Pathology, SA Pathology RCV002272472 SCV002556805 likely benign Familial cancer of breast 2020-05-25 criteria provided, single submitter clinical testing The BRCA2 c.10013C>A variant is classified as Likely Benign (BS2, BP6) Rebbeck 2016 excluded PTC variants after codon 3010 and did not define as pathogenic; ENIGMA criteria (2017) - variants downstream of position 3326 "unlikely clinically relevant". Case-control and frequency data indicate that BRCA2 c.9976A>T (p.Lys3326Ter) does not confer a high risk of cancer (OR 1.3-1.5, dependent on breast or ovarian cancer subtype (Meeks et al., 2016; J Natl Cancer Inst 108), demonstrating that residues at and downstream of 3327 are likely dispensable.
GeneDx RCV003327517 SCV004034935 uncertain significance not provided 2023-03-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation as the last 81 amino acids are lost; Located in a region that tolerates variation and lacks pathogenic variants; Has not been previously published as pathogenic or benign to our knowledge; Also known as 10241C>A
Ambry Genetics RCV004038643 SCV005023831 likely benign Hereditary cancer-predisposing syndrome 2023-10-25 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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