ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3166C>G (p.Gln1056Glu)

dbSNP: rs79728106
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985494 SCV001133742 uncertain significance not provided 2024-02-15 criteria provided, single submitter clinical testing The BRCA2 c.3166C>G (p.Gln1056Glu) variant has been reported in the published literature in an individual with lung cancer (PMID: 29106415 (2017)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, 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 predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001858622 SCV002223425 uncertain significance Hereditary breast ovarian cancer syndrome 2021-02-03 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 801101). 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. 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. This sequence change replaces glutamine with glutamic acid at codon 1056 of the BRCA2 protein (p.Gln1056Glu). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is not present in population databases (ExAC no frequency).
Ambry Genetics RCV002320198 SCV002609757 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-28 criteria provided, single submitter clinical testing The p.Q1056E variant (also known as c.3166C>G), located in coding exon 10 of the BRCA2 gene, results from a C to G substitution at nucleotide position 3166. The glutamine at codon 1056 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is not well 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 RCV002320198 SCV003851730 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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