ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6050A>G (p.Lys2017Arg)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003645407 SCV004376816 uncertain significance Hereditary breast ovarian cancer syndrome 2025-01-07 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 2017 of the BRCA2 protein (p.Lys2017Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2781616). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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 RCV004371518 SCV005028532 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-21 criteria provided, single submitter clinical testing The p.K2017R variant (also known as c.6050A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 6050. The lysine at codon 2017 is replaced by arginine, an amino acid with highly similar properties. This alteration was identified amongst a cohort of 3984 Chinese women with a breast cancer diagnosis undergoing BRCA1/2 genetic testing (Yao L et al. J Hum Genet, 2022 Nov;67:639-642). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.