ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2372A>T (p.Asp791Val) (rs876658934)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216036 SCV000274798 uncertain significance Hereditary cancer-predisposing syndrome 2015-03-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000216036 SCV000689333 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-20 criteria provided, single submitter clinical testing
GeneDx RCV000478836 SCV000566878 uncertain significance not provided 2018-09-05 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.2372A>T at the cDNA level, p.Asp791Val (D791V) at the protein level, and results in the change of an Aspartic Acid to a Valine (GAT>GTT). This variant has been observed in at least one individual with serous ovarian cancer (Ramus 2015). BRIP1 Asp791Val was not observed 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 Asp791Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000461754 SCV000547232 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-11-30 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with valine at codon 791 of the BRIP1 protein (p.Asp791Val). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in an individual affected with ovarian cancer (PMID: 26315354). ClinVar contains an entry for this variant (Variation ID: 231061). 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 and their clinical significance is uncertain. In summary, this variant has uncertain impact on BRIP1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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