ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1504A>C (p.Lys502Gln)

dbSNP: rs276174809
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160038 SCV000210271 uncertain significance not provided 2024-03-08 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 1732A>C; This variant is associated with the following publications: (PMID: 32377563, 35264596, 29884841, 26997744)
Ambry Genetics RCV000223354 SCV000276062 likely benign Hereditary cancer-predisposing syndrome 2018-03-15 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 RCV000637723 SCV000759196 uncertain significance Hereditary breast ovarian cancer syndrome 2023-12-29 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 502 of the BRCA2 protein (p.Lys502Gln). This variant is present in population databases (rs276174809, gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 10923033, 26997744, 35264596). ClinVar contains an entry for this variant (Variation ID: 125946). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae 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.
Color Diagnostics, LLC DBA Color Health RCV000223354 SCV000911441 benign Hereditary cancer-predisposing syndrome 2016-10-06 criteria provided, single submitter clinical testing
Mendelics RCV000112928 SCV001139001 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2019-05-28 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000223354 SCV003851439 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).
Breast Cancer Information Core (BIC) (BRCA2) RCV000112928 SCV000145879 benign Breast-ovarian cancer, familial, susceptibility to, 2 2010-12-17 no assertion criteria provided clinical testing

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