ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7953G>C (p.Arg2651Ser)

dbSNP: rs752351454
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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 RCV000795905 SCV000935386 uncertain significance Hereditary breast ovarian cancer syndrome 2018-12-16 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 2651 of the BRCA2 protein (p.Arg2651Ser). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV001026992 SCV001189478 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-25 criteria provided, single submitter clinical testing The p.R2651S variant (also known as c.7953G>C), located in coding exon 16 of the BRCA2 gene, results from a G to C substitution at nucleotide position 7953. The arginine at codon 2651 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478493 SCV004220577 uncertain significance not provided 2023-03-17 criteria provided, single submitter clinical testing The variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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