Submissions for variant NM_032043.3(BRIP1):c.886G>C (p.Glu296Gln)

gnomAD frequency: 0.00003  dbSNP: rs876660125

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000214417	SCV000277291	uncertain significance	Hereditary cancer-predisposing syndrome	2024-05-27	criteria provided, single submitter	clinical testing	The p.E296Q variant (also known as c.886G>C), located in coding exon 6 of the BRIP1 gene, results from a G to C substitution at nucleotide position 886. The glutamic acid at codon 296 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000636125	SCV000757557	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2025-02-02	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 296 of the BRIP1 protein (p.Glu296Gln). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 233003). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRIP1 protein function. 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	RCV000214417	SCV001340987	uncertain significance	Hereditary cancer-predisposing syndrome	2021-03-05	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with glutamine at codon 296 of the BRIP1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 been identified in 1/31400 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.
Sema4, Sema4	RCV000214417	SCV002529243	uncertain significance	Hereditary cancer-predisposing syndrome	2021-09-12	criteria provided, single submitter	curation
GeneDx	RCV002281070	SCV002569784	uncertain significance	not provided	2022-08-18	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences	RCV004529379	SCV004109227	uncertain significance	BRIP1-related disorder	2022-09-01	criteria provided, single submitter	clinical testing	The BRIP1 c.886G>C variant is predicted to result in the amino acid substitution p.Glu296Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.011% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-59885860-C-G) and has been interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/233003). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics	RCV003462509	SCV004217069	uncertain significance	Familial cancer of breast	2023-06-28	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000214417	SCV005045457	uncertain significance	Hereditary cancer-predisposing syndrome	2024-03-12	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005055769	SCV005726794	uncertain significance	not specified	2024-11-11	criteria provided, single submitter	clinical testing