ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4738T>C (p.Cys1580Arg)

dbSNP: rs2072511910
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001305948 SCV001495302 uncertain significance Hereditary breast ovarian cancer syndrome 2021-07-16 criteria provided, single submitter clinical testing 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 arginine 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. This variant has not been reported in the literature in individuals with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with arginine at codon 1580 of the BRCA2 protein (p.Cys1580Arg). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and arginine. 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.
Ambry Genetics RCV002341610 SCV002635939 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-25 criteria provided, single submitter clinical testing The p.C1580R variant (also known as c.4738T>C), located in coding exon 10 of the BRCA2 gene, results from a T to C substitution at nucleotide position 4738. The cysteine at codon 1580 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington RCV002341610 SCV003852060 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).

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