ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2393G>A (p.Arg798Gln) (rs375082407)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132435 SCV000187529 uncertain significance Hereditary cancer-predisposing syndrome 2014-03-10 criteria provided, single submitter clinical testing
Color RCV000132435 SCV000684210 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-13 criteria provided, single submitter clinical testing
Counsyl RCV000662702 SCV000785448 uncertain significance Fanconi anemia, complementation group J; Neoplasm of ovary 2017-08-11 criteria provided, single submitter clinical testing
GeneDx RCV000220012 SCV000279854 uncertain significance not provided 2018-07-13 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.2393G>A at the cDNA level, p.Arg798Gln (R798Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). Although this variant has not been reported as a germline variant to our knowledge, BRIP1 Arg798Gln has been reported as a somatic variant in a colorectal carcinoma and a cutaneous squamous cell carcinoma (Cancer Genome 2012, Pickering 2014). BRIP1 Arg798Gln 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 Arg798Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000475477 SCV000547291 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-09-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 798 of the BRIP1 protein (p.Arg798Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs375082407, ExAC 0.02%). This variant has not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 142949). 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: "Possibly 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.

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