ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.2606A>G (p.Gln869Arg)

gnomAD frequency: 0.00002  dbSNP: rs1060501733
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000461585 SCV000547249 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2023-12-29 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 869 of the BRIP1 protein (p.Gln869Arg). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with ovarian cancer (PMID: 26315354). ClinVar contains an entry for this variant (Variation ID: 407799). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRIP1 protein function with a negative predictive value of 80%. 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.
Color Diagnostics, LLC DBA Color Health RCV000775728 SCV000910151 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV000775728 SCV001176950 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-25 criteria provided, single submitter clinical testing The p.Q869R variant (also known as c.2606A>G), located in coding exon 18 of the BRIP1 gene, results from an A to G substitution at nucleotide position 2606. The glutamine at codon 869 is replaced by arginine, an amino acid with highly similar properties. In one study, this alteration was observed in 1/3236 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 well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV002275040 SCV002562534 uncertain significance not provided 2022-02-09 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with ovarian cancer in published literature (Ramus 2015); This variant is associated with the following publications: (PMID: 26315354)
Baylor Genetics RCV003463893 SCV004217077 uncertain significance Familial cancer of breast 2023-06-21 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV004596190 SCV005089829 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing

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