ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2911T>A (p.Leu971Ile)

dbSNP: rs1555282936
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000534263 SCV000635256 uncertain significance Hereditary breast ovarian cancer syndrome 2017-05-26 criteria provided, single submitter clinical testing This sequence change replaces leucine with isoleucine at codon 971 of the BRCA2 protein (p.Leu971Ile). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a BRCA2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on BRCA2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002438339 SCV002750976 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-17 criteria provided, single submitter clinical testing The p.L971I variant (also known as c.2911T>A), located in coding exon 10 of the BRCA2 gene, results from a T to A substitution at nucleotide position 2911. The leucine at codon 971 is replaced by isoleucine, an amino acid with highly 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV002438339 SCV003850229 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.