Submissions for variant NM_032043.3(BRIP1):c.15G>C (p.Trp5Cys)

dbSNP: rs2078973424

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001319299	SCV001510039	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2020-05-21	criteria provided, single submitter	clinical testing	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. 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 cysteine 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 tryptophan with cysteine at codon 5 of the BRIP1 protein (p.Trp5Cys). The tryptophan residue is weakly conserved and there is a large physicochemical difference between tryptophan and cysteine.