ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.838A>C (p.Lys280Gln)

dbSNP: rs80359085
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001188159 SCV001355136 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-19 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamine at codon 280 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV001188159 SCV003848068 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 RCV001188159 SCV004052610 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-11 criteria provided, single submitter clinical testing The p.K280Q variant (also known as c.838A>C), located in coding exon 9 of the BRCA2 gene, results from an A to C substitution at nucleotide position 838. The lysine at codon 280 is replaced by glutamine, an amino acid with similar properties. This amino acid position is conserved. 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.

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