ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2882A>T (p.Gln961Leu)

dbSNP: rs2072467086
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001177746 SCV001342009 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-04 criteria provided, single submitter clinical testing This missense variant replaces glutamine with leucine at codon 961 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002558860 SCV003265386 uncertain significance Hereditary breast ovarian cancer syndrome 2021-12-23 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 919510). 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. 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. This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 961 of the BRCA2 protein (p.Gln961Leu).
University of Washington Department of Laboratory Medicine, University of Washington RCV001177746 SCV003850205 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 RCV001177746 SCV005548679 uncertain significance Hereditary cancer-predisposing syndrome 2024-07-31 criteria provided, single submitter clinical testing The p.Q961L variant (also known as c.2882A>T), located in coding exon 10 of the BRCA2 gene, results from an A to T substitution at nucleotide position 2882. The glutamine at codon 961 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is 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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