Submissions for variant NM_032043.3(BRIP1):c.3065A>T (p.Glu1022Val)

dbSNP: rs2144089594

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001804596	SCV002053366	uncertain significance	Hereditary cancer-predisposing syndrome	2021-11-12	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with valine at codon 1022 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001869520	SCV002204394	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2021-06-20	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRIP1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with valine at codon 1022 of the BRIP1 protein (p.Glu1022Val). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and valine. 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.