Submissions for variant NM_032043.3(BRIP1):c.37G>A (p.Val13Met)

dbSNP: rs1488264110

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001976253	SCV002264948	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2021-08-23	criteria provided, single submitter	clinical testing	This sequence change replaces valine with methionine at codon 13 of the BRIP1 protein (p.Val13Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics	RCV002361334	SCV002624730	uncertain significance	Hereditary cancer-predisposing syndrome	2022-03-16	criteria provided, single submitter	clinical testing	The p.V13M variant (also known as c.37G>A), located in coding exon 1 of the BRIP1 gene, results from a G to A substitution at nucleotide position 37. The valine at codon 13 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
Color Diagnostics, LLC DBA Color Health	RCV002361334	SCV004360315	uncertain significance	Hereditary cancer-predisposing syndrome	2022-08-22	criteria provided, single submitter	clinical testing	This missense variant replaces valine with methionine at codon 13 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 been identified in 1/251314 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.