Submissions for variant NM_032043.3(BRIP1):c.2405A>G (p.Asp802Gly)

dbSNP: rs876660273

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000222483	SCV000277565	uncertain significance	Hereditary cancer-predisposing syndrome	2022-07-21	criteria provided, single submitter	clinical testing	The p.D802G variant (also known as c.2405A>G), located in coding exon 16 of the BRIP1 gene, results from an A to G substitution at nucleotide position 2405. The aspartic acid at codon 802 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.D802G remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000548413	SCV000633609	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2022-02-08	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 802 of the BRIP1 protein (p.Asp802Gly). ClinVar contains an entry for this variant (Variation ID: 233229). 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: "Deleterious"; 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000781184	SCV000919066	uncertain significance	not specified	2018-11-05	criteria provided, single submitter	clinical testing	Variant summary: BRIP1 c.2405A>G (p.Asp802Gly) results in a non-conservative amino acid change located in the ATP-dependent helicase, C-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 244614 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2405A>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and both laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.