Submissions for variant NM_032043.3(BRIP1):c.2948T>A (p.Ile983Asn)

gnomAD frequency: 0.00001  dbSNP: rs587781417

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129283	SCV000184044	likely benign	Hereditary cancer-predisposing syndrome	2023-12-06	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Counsyl	RCV000412403	SCV000489975	uncertain significance	Fanconi anemia complementation group J	2016-09-06	criteria provided, single submitter	clinical testing
Counsyl	RCV000409964	SCV000489976	uncertain significance	Ovarian neoplasm	2016-09-06	criteria provided, single submitter	clinical testing
Invitae	RCV000636117	SCV000757549	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2023-12-21	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 983 of the BRIP1 protein (p.Ile983Asn). This variant is present in population databases (rs587781417, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 140985). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Color Diagnostics, LLC DBA Color Health	RCV000129283	SCV000911638	uncertain significance	Hereditary cancer-predisposing syndrome	2019-01-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001775619	SCV002013970	uncertain significance	not provided	2019-07-08	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26921362, 26315354)
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001775619	SCV002046345	uncertain significance	not provided	2020-10-26	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003315873	SCV004019401	uncertain significance	Familial cancer of breast	2023-03-01	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.