ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.103G>A (p.Gly35Arg)

gnomAD frequency: 0.00001  dbSNP: rs373104267
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001344286 SCV001538327 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2022-07-24 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 35 of the BRIP1 protein (p.Gly35Arg). This variant is present in population databases (rs373104267, gnomAD 0.007%). 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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1040610). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002282525 SCV002571913 uncertain significance not specified 2022-08-09 criteria provided, single submitter clinical testing Variant summary: BRIP1 c.103G>A (p.Gly35Arg) results in a non-conservative amino acid change located in the Helicase-like, DEXD box c2 type domain (IPR006554) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251350 control chromosomes. 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.103G>A in individuals affected with Breast/Ovarian/BRIP1-related 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.
Ambry Genetics RCV002395754 SCV002702672 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-18 criteria provided, single submitter clinical testing The p.G35R variant (also known as c.103G>A), located in coding exon 2 of the BRIP1 gene, results from a G to A substitution at nucleotide position 103. The glycine at codon 35 is replaced by arginine, an amino acid with dissimilar properties. In one study, this alteration was observed in 0/3236 cases with invasive epithelial ovarian cancer and 0/3431 controls (Ramus SJ et al. J Natl Cancer Inst, 2015 Nov;107:). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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