ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6821G>A (p.Gly2274Glu)

dbSNP: rs55712212
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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 RCV000698869 SCV000827558 uncertain significance Hereditary breast ovarian cancer syndrome 2018-04-30 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 2274 of the BRCA2 protein (p.Gly2274Glu). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant has been reported in an individual in the Leiden Open-source Variation Database (PMID: 21520333). 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: "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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003158053 SCV003847480 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 RCV003158053 SCV005548703 uncertain significance Hereditary cancer-predisposing syndrome 2024-08-20 criteria provided, single submitter clinical testing The p.G2274E variant (also known as c.6821G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 6821. The glycine at codon 2274 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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