ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8164A>G (p.Thr2722Ala)

dbSNP: rs1555287019
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
Ambry Genetics RCV000561836 SCV000661383 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-29 criteria provided, single submitter clinical testing The p.T2722A variant (also known as c.8164A>G), located in coding exon 17 of the BRCA2 gene, results from an A to G substitution at nucleotide position 8164. The threonine at codon 2722 is replaced by alanine, an amino acid with similar properties. This variant was non-functional in a homology-directed DNA repair (HDR) assay (Richardson ME et al. Am J Hum Genet, 2021 03;108:458-468). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001213108 SCV001384725 likely pathogenic Hereditary breast ovarian cancer syndrome 2023-07-06 criteria provided, single submitter clinical testing Experimental studies have shown that this missense change affects BRCA2 function (PMID: 33609447). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Thr2722 amino acid residue in BRCA2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12145750, 18607349, 23108138, 25146914). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33609447) did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA2 function. ClinVar contains an entry for this variant (Variation ID: 479367). 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 threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 2722 of the BRCA2 protein (p.Thr2722Ala).
GeneDx RCV004787901 SCV005401774 likely pathogenic not provided 2024-05-15 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals with a personal and/or family history of breast and/or ovarian cancer (PMID: 35534704); In silico analysis indicates that this missense variant does not alter protein structure/function; Also known as 8392A>G; This variant is associated with the following publications: (PMID: 33609447, 12228710, 35736817, 35534704)

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.