ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1555A>G (p.Ser519Gly)

dbSNP: rs1555281950
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000555286 SCV000635169 uncertain significance Hereditary breast ovarian cancer syndrome 2022-07-19 criteria provided, single submitter clinical testing 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 serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 519 of the BRCA2 protein (p.Ser519Gly). ClinVar contains an entry for this variant (Variation ID: 462239). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Color Diagnostics, LLC DBA Color Health RCV000580014 SCV000683430 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-22 criteria provided, single submitter clinical testing
Liquid Biopsy and Cancer Interception Group, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research RCV001090206 SCV001245504 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000580014 SCV003851480 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).
Neuberg Centre For Genomic Medicine, NCGM RCV001090206 SCV004046952 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 criteria provided, single submitter clinical testing The missense variant in c.1555A>G (p.Ser519Gly) in BRCA2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ser519Gly variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Variant of Uncertain Significance. The amino acid Ser at position 519 is changed to a Gly changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Ser519Gly in BRCA2 is predicted as conserved by GERP++. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS)

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.