ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1040A>C (p.Gln347Pro)

dbSNP: rs55800493
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167323 SCV000218173 likely benign Hereditary cancer-predisposing syndrome 2014-12-22 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758856 SCV000887743 uncertain significance not provided 2018-01-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001201830 SCV001372921 uncertain significance Hereditary breast ovarian cancer syndrome 2025-01-12 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 347 of the BRCA2 protein (p.Gln347Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 32772980). ClinVar contains an entry for this variant (Variation ID: 187583). 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000167323 SCV003849800 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).

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.