ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6351T>G (p.Cys2117Trp)

dbSNP: rs876659368
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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 RCV000538226 SCV000635505 uncertain significance Hereditary breast ovarian cancer syndrome 2017-06-07 criteria provided, single submitter clinical testing In summary, this variant has uncertain impact on BRCA2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces cysteine with tryptophan at codon 2117 of the BRCA2 protein (p.Cys2117Trp). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a BRCA2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0").
Ambry Genetics RCV002367823 SCV002661408 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-03 criteria provided, single submitter clinical testing The p.C2117W variant (also known as c.6351T>G), located in coding exon 10 of the BRCA2 gene, results from a T to G substitution at nucleotide position 6351. The cysteine at codon 2117 is replaced by tryptophan, 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 RCV002367823 SCV003852455 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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