ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4739G>A (p.Cys1580Tyr)

dbSNP: rs398122784
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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 RCV001346041 SCV001540202 uncertain significance Hereditary breast ovarian cancer syndrome 2020-05-29 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 91824). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 1580 of the BRCA2 protein (p.Cys1580Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tyrosine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain.
GeneDx RCV001762202 SCV002008890 uncertain significance not provided 2021-06-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as germline pathogenic or benign to our knowledge; Also known as 4967G>A; This variant is associated with the following publications: (PMID: 11948477, 27535533)
University of Washington Department of Laboratory Medicine, University of Washington RCV003157401 SCV003852061 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).
Sharing Clinical Reports Project (SCRP) RCV000077732 SCV000109535 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2008-06-17 no assertion criteria provided clinical testing

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