ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6766T>C (p.Cys2256Arg)

dbSNP: rs559106452
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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 RCV000820020 SCV000960712 uncertain significance Hereditary breast ovarian cancer syndrome 2024-01-10 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 2256 of the BRCA2 protein (p.Cys2256Arg). This variant is present in population databases (rs559106452, gnomAD 0.006%). 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: 662390). 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003158236 SCV003847434 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).
Ambry Genetics RCV003158236 SCV004063316 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-23 criteria provided, single submitter clinical testing The p.C2256R variant (also known as c.6766T>C), located in coding exon 10 of the BRCA2 gene, results from a T to C substitution at nucleotide position 6766. The cysteine at codon 2256 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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