Submissions for variant NM_032043.3(BRIP1):c.307G>A (p.Gly103Arg)

dbSNP: rs777068696

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000636148	SCV000757580	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2019-11-09	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 arginine 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 disease. This variant is present in population databases (rs777068696, ExAC 0.009%). This sequence change replaces glycine with arginine at codon 103 of the BRIP1 protein (p.Gly103Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine.