ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.3605A>G (p.Glu1202Gly) (rs776010326)

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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 RCV000165933 SCV000216689 uncertain significance Hereditary cancer-predisposing syndrome 2016-05-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Color RCV000165933 SCV000684268 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-23 criteria provided, single submitter clinical testing
GeneDx RCV000214877 SCV000278906 uncertain significance not provided 2019-01-07 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.3605A>G at the cDNA level, p.Glu1202Gly (E1202G) at the protein level, and results in the change of a Glutamic Acid to a Glycine (GAA>GGA). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. BRIP1 Glu1202Gly 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 that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRIP1 Glu1202Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000233466 SCV000291045 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-09-18 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 1202 of the BRIP1 protein (p.Glu1202Gly). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (ExAC <0.01%) but has not been reported in the literature in individuals with a BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 186352). 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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