ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1883G>T (p.Gly628Val) (rs1064794907)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478238 SCV000570187 uncertain significance not provided 2016-10-31 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.1883G>T at the cDNA level, p.Gly628Val (G628V) at the protein level, and results in the change of a Glycine to a Valine (GGT>GTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Gly628Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glycine and Valine share similar properties, this is considered a conservative amino acid substitution. BRIP1 Gly628Val occurs at a position that is conserved across species and is located in the helicase domain (Cantor 2011). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether BRIP1 Gly628Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000818704 SCV000959330 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-11-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 628 of the BRIP1 protein (p.Gly628Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 421095). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably 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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