ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.10083A>C (p.Gln3361His)

dbSNP: rs1593202272
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001208206 SCV001379583 uncertain significance Hereditary breast ovarian cancer syndrome 2021-01-19 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 3361 of the BRCA2 protein (p.Gln3361His). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and histidine.
All of Us Research Program, National Institutes of Health RCV004807462 SCV005425873 uncertain significance BRCA2-related cancer predisposition 2024-04-16 criteria provided, single submitter clinical testing This missense variant replaces glutamine with histidine at codon 3361 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.

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