ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.888G>C (p.Glu296Asp)

dbSNP: rs876658249
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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 RCV000221644 SCV000273248 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-26 criteria provided, single submitter clinical testing The p.E296D variant (also known as c.888G>C), located in coding exon 6 of the BRIP1 gene, results from a G to C substitution at nucleotide position 888. The glutamic acid at codon 296 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000229608 SCV000291061 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2023-12-04 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 296 of the BRIP1 protein (p.Glu296Asp). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 229882). 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 RCV000221644 SCV001345204 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-01 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with aspartic acid at codon 296 of the BRIP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in 0/13,213 individuals affected with breast cancer and 1/5242 control individuals in a case-control study (PMID: 26921362). This variant has been identified in 1/250888 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Baylor Genetics RCV003462415 SCV004217058 uncertain significance Familial cancer of breast 2023-07-13 criteria provided, single submitter clinical testing

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