ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1471A>G (p.Thr491Ala)

dbSNP: rs1566223650
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
Mendelics RCV000709298 SCV000838755 uncertain significance Hereditary breast ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Mendelics RCV000989000 SCV001138998 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV001011762 SCV001172121 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-14 criteria provided, single submitter clinical testing The p.T491A variant (also known as c.1471A>G), located in coding exon 9 of the BRCA2 gene, results from an A to G substitution at nucleotide position 1471. The threonine at codon 491 is replaced by alanine, an amino acid with similar properties. 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.
Invitae RCV000709298 SCV002593761 uncertain significance Hereditary breast ovarian cancer syndrome 2022-08-03 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 491 of the BRCA2 protein (p.Thr491Ala). 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: 584847). 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. 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 RCV001011762 SCV003851416 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.