ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.10120A>G (p.Thr3374Ala) (rs80358395)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000043717 SCV000071730 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-10-27 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 3374 of the BRCA2 protein (p.Thr3374Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with hepatocellular carcinoma (Invitae). However, in that individual pathogenic allele[s] were also identified in BRCA2, which suggests that this c.10120A>G variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 51046). 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, 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.
Ambry Genetics RCV000166051 SCV000216812 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-22 criteria provided, single submitter clinical testing The p.T3374A variant (also known as c.10120A>G), located in coding exon 26 of the BRCA2 gene, results from an A to G substitution at nucleotide position 10120. The threonine at codon 3374 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.
Counsyl RCV000112843 SCV000488691 uncertain significance Breast-ovarian cancer, familial 2 2016-05-23 criteria provided, single submitter clinical testing
Color Health, Inc RCV000166051 SCV000911251 likely benign Hereditary cancer-predisposing syndrome 2017-02-17 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284405 SCV001470188 uncertain significance not provided 2019-11-15 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000112843 SCV000145756 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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.