ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1490C>T (p.Ser497Leu)

dbSNP: rs1064794018
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486670 SCV000567599 uncertain significance not provided 2025-01-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 1718C>T; This variant is associated with the following publications: (PMID: 25925381, 29884841, 38664720, 32377563)
Color Diagnostics, LLC DBA Color Health RCV000773057 SCV000906467 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000773057 SCV001172247 likely benign Hereditary cancer-predisposing syndrome 2024-11-08 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001050810 SCV001214935 uncertain significance Hereditary breast ovarian cancer syndrome 2025-01-19 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 497 of the BRCA2 protein (p.Ser497Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 419653). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
University of Washington Department of Laboratory Medicine, University of Washington RCV000773057 SCV003851428 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Fulgent Genetics, Fulgent Genetics RCV005010389 SCV005634408 uncertain significance Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3; Familial prostate cancer 2024-06-18 criteria provided, single submitter clinical testing

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