ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2012A>G (p.Glu671Gly) (rs587778135)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000214355 SCV000272994 uncertain significance Hereditary cancer-predisposing syndrome 2014-11-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000767211 SCV000279823 uncertain significance not provided 2016-01-22 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.2012A>G at the cDNA level, p.Glu671Gly (E671G) at the protein level, and results in the change of a Glutamic Acid to a Glycine (GAG>GGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Glu671Gly 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 Glutamic Acid and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRIP1 Glu671Gly 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 Glu671Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000636172 SCV000757604 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-03-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 671 of the BRIP1 protein (p.Glu671Gly). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and glycine. 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. ClinVar contains an entry for this variant (Variation ID: 133750). 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.
ITMI RCV000120394 SCV000084546 not provided not specified 2013-09-19 no assertion provided reference population

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