Submissions for variant NM_032043.3(BRIP1):c.2923G>A (p.Glu975Lys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002439985	SCV002751045	uncertain significance	Hereditary cancer-predisposing syndrome	2022-08-09	criteria provided, single submitter	clinical testing	The p.E975K variant (also known as c.2923G>A), located in coding exon 19 of the BRIP1 gene, results from a G to A substitution at nucleotide position 2923. The glutamic acid at codon 975 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. 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.
Color Diagnostics, LLC DBA Color Health	RCV002439985	SCV004362895	uncertain significance	Hereditary cancer-predisposing syndrome	2023-10-09	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with lysine at codon 975 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 BRIP1-related disorders 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.