ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.297C>G (p.Asp99Glu) (rs201617644)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000698838 SCV000827527 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-11-28 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 99 of the BRIP1 protein (p.Asp99Glu). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRIP1-related disease. 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 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.
Integrated Genetics/Laboratory Corporation of America RCV000781182 SCV000919064 uncertain significance not specified 2018-10-22 criteria provided, single submitter clinical testing Variant summary: BRIP1 c.297C>G (p.Asp99Glu) results in a conservative amino acid change located in the ATP-binding domain (IPR014001) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 277200 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.297C>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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