ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2728G>C (p.Glu910Gln) (rs1007808618)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484483 SCV000564816 uncertain significance not provided 2015-02-03 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.2728G>C at the cDNA level, p.Glu910Gln (E910Q) at the protein level, and results in the change of a Glutamic Acid to a Glutamine (GAA>CAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Glu910Gln was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Glutamic Acid and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. BRIP1 Glu910Gln occurs at a position that is poorly conserved across species and is located in the BRCA1 interaction region (UniProt, Cantor 2011). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRIP1 Glu910Gln is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000563513 SCV000661578 uncertain significance Hereditary cancer-predisposing syndrome 2016-12-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000817172 SCV000957718 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glutamine at codon 910 of the BRIP1 protein (p.Glu910Gln). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and glutamine. 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: 418098). 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.

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