ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3904A>G (p.Thr1302Ala) (rs543339423)

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
Ambry Genetics RCV000130823 SCV000185719 uncertain significance Hereditary cancer-predisposing syndrome 2017-02-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000255972 SCV000321457 uncertain significance not provided 2018-10-18 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.3904A>G at the cDNA level, p.Thr1302Ala (T1302A) at the protein level, and results in the change of a Threonine to an Alanine (ACT>GCT). Using alternate nomenclature, this variant would be defined as BRCA2 4132A>G. This variant has been identified in at least one individual with a personal and family history of breast and/or ovarian cancer (Cao 2016). BRCA2 Thr1302Ala was not observed in large population cohorts (Lek 2016). This variant is located in the RAD51 binding domain (Roy 2012). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRCA2 Thr1302Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000663001 SCV000786005 uncertain significance Breast-ovarian cancer, familial 2 2018-02-06 criteria provided, single submitter clinical testing
Invitae RCV000698088 SCV000826731 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-28 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 1302 of the BRCA2 protein (p.Thr1302Ala). The threonine residue is moderately 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 reported in an individual with a personal and/or family history of breast and/or ovarian cancer (PMID: 26852015). ClinVar contains an entry for this variant (Variation ID: 142030). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Color RCV000130823 SCV000911187 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-26 criteria provided, single submitter 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.