ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.634G>A (p.Gly212Ser)

dbSNP: rs1555609387
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000584189 SCV000689407 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-12 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 212 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 not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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.
Ambry Genetics RCV000584189 SCV001187304 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-22 criteria provided, single submitter clinical testing The p.G212S variant (also known as c.634G>A), located in coding exon 6 of the BRIP1 gene, results from a G to A substitution at nucleotide position 634. The glycine at codon 212 is replaced by serine, an amino acid with similar properties. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001221914 SCV001393985 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2023-12-16 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 212 of the BRIP1 protein (p.Gly212Ser). This variant is not present in population databases (gnomAD no frequency). 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: 491475). 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.

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