ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1198G>T (p.Asp400Tyr) (rs764711572)

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
Invitae RCV000196847 SCV000255145 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-12-17 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with tyrosine at codon 400 of the BRIP1 protein (p.Asp400Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is present in population databases (rs764711572, ExAC 0.002%). This variant has been reported in an individual with suspected Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 216785). 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 disruptive, but these predictions have not been confirmed by published functional studies. 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 RCV000215891 SCV000275090 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-11 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000219685 SCV000278896 uncertain significance not provided 2018-11-13 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.1198G>T at the cDNA level, p.Asp400Tyr (D400Y) at the protein level, and results in the change of an Aspartic Acid to a Tyrosine (GAC>TAC). This variant was observed in an individual undergoing multigene cancer panel testing due to a history of a Lynch syndrome-related cancer and/or polyps (Yurgelun 2015). BRIP1 Asp400Tyr 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 Asp400Tyr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000215891 SCV000689254 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-03 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.