ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6152A>G (p.Asn2051Ser)

dbSNP: rs398122549
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000203759 SCV000261478 uncertain significance Hereditary breast ovarian cancer syndrome 2023-03-09 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 2051 of the BRCA2 protein (p.Asn2051Ser). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 29470806). 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: 91439).
Ambry Genetics RCV000222229 SCV000275243 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-03 criteria provided, single submitter clinical testing The p.N2051S variant (also known as c.6152A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 6152. The asparagine at codon 2051 is replaced by serine, an amino acid with highly similar properties. This alteration has been reported as a variant of unknown significance in a cohort of 1010 unrelated patients and families from across India with an indication of breast and/or ovarian cancers (Singh J et al. Breast Cancer Res. Treat., 2018 Jul;170:189-196). 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.
Color Diagnostics, LLC DBA Color Health RCV000222229 SCV000906130 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-05 criteria provided, single submitter clinical testing
Mendelics RCV000076956 SCV001139138 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2019-05-28 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000222229 SCV003850980 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).
All of Us Research Program, National Institutes of Health RCV000076956 SCV004846711 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2022-12-16 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000076956 SCV000108753 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2006-09-01 no assertion criteria provided clinical testing

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.