ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1051A>G (p.Lys351Glu)

dbSNP: rs1003779807
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000775857 SCV000910331 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000775857 SCV001178168 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-16 criteria provided, single submitter clinical testing The p.K351E variant (also known as c.1051A>G), located in coding exon 9 of the BRCA2 gene, results from an A to G substitution at nucleotide position 1051. The lysine at codon 351 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is poorly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002304219 SCV002590917 uncertain significance Hereditary breast ovarian cancer syndrome 2022-08-22 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. 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. ClinVar contains an entry for this variant (Variation ID: 630465). 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 lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 351 of the BRCA2 protein (p.Lys351Glu).
University of Washington Department of Laboratory Medicine, University of Washington RCV000775857 SCV003849804 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).
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV005055135 SCV005689372 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2024-08-27 criteria provided, single submitter clinical testing The BRCA2 c.1051A>G (p.Lys351Glu) missense variant is absent in gnomAD v2.1.1. The in silico tool BayesDel and splicing algorithm(s) predict a benign effect, but to our knowledge these predictions have not been confirmed by functional studies. To our knowledge, this variant has not been reported in the literature in individuals with hereditary breast and ovarian cancer or Fanconi anemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

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.