ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3885A>C (p.Gln1295His)

dbSNP: rs876659864
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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 RCV000637593 SCV000759059 uncertain significance Hereditary breast ovarian cancer syndrome 2017-12-25 criteria provided, single submitter clinical testing 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. This variant has not been reported in the literature in individuals with BRCA2-related disease. This sequence change replaces glutamine with histidine at codon 1295 of the BRCA2 protein (p.Gln1295His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. This variant is not present in population databases (ExAC no frequency).
University of Washington Department of Laboratory Medicine, University of Washington RCV003157771 SCV003848499 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 RCV003157771 SCV005550093 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-16 criteria provided, single submitter clinical testing The p.Q1295H variant (also known as c.3885A>C), located in coding exon 10 of the BRCA2 gene, results from an A to C substitution at nucleotide position 3885. The glutamine at codon 1295 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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