ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1984G>A (p.Ala662Thr) (rs571340013)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167392 SCV000218246 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000168048 SCV000218701 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 662 of the BRIP1 protein (p.Ala662Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with breast cancer (PMID: 25452441). ClinVar contains an entry for this variant (Variation ID: 187645). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
GeneDx RCV000521753 SCV000616665 uncertain significance not provided 2018-01-23 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.1984G>A at the cDNA level, p.Ala662Thr (A662T) at the protein level, and results in the change of an Alanine to a Threonine (GCT>ACT). This variant was observed in an individual with triple negative breast cancer (Couch 2015). BRIP1 Ala662Thr was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In-silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRIP1 Ala662Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000167392 SCV000684175 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-18 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.