ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6310A>C (p.Lys2104Gln)

dbSNP: rs1555284629
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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 RCV000528876 SCV000635504 uncertain significance Hereditary breast ovarian cancer syndrome 2017-07-19 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamine at codon 2104 of the BRCA2 protein (p.Lys2104Gln). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. 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 glutamine 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. 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.
Ambry Genetics RCV002367822 SCV002660601 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-02 criteria provided, single submitter clinical testing The p.K2104Q variant (also known as c.6310A>C), located in coding exon 10 of the BRCA2 gene, results from an A to C substitution at nucleotide position 6310. The lysine at codon 2104 is replaced by glutamine, an amino acid with 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 RCV002367822 SCV003852413 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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