ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.316C>A (p.Arg106Ser) (rs587780247)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000216303 SCV000279750 uncertain significance not provided 2015-12-30 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.316C>A at the cDNA level, p.Arg106Ser (R106S) at the protein level, and results in the change of an Arginine to a Serine (CGT>AGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Arg106Ser 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 Arginine and Serine differ in some properties, this is considered a semi-conservative amino acid substitution. BRIP1 Arg106Ser occurs at a position that is not conserved and is located in the helicase domain (Cantor 2011). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRIP1 Arg106Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000526478 SCV000633653 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2017-05-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 106 of the BRIP1 protein (p.Arg106Ser). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a BRIP1-related disease. However, it been found in an unaffected control individual (PMID: 26921362). ClinVar contains an entry for this variant (Variation ID: 234737). 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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