Submissions for variant NM_032043.3(BRIP1):c.778A>G (p.Thr260Ala)

gnomAD frequency: 0.00002  dbSNP: rs138743097

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000123365	SCV000166688	likely benign	Familial cancer of breast; Fanconi anemia complementation group J	2024-01-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000586716	SCV000210869	likely benign	not provided	2020-12-01	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26315354, 28135145, 26976419, 26921362, 28076423, 28968953, 29641532, 32959997)
Ambry Genetics	RCV000160362	SCV000215637	likely benign	Hereditary cancer-predisposing syndrome	2019-03-30	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586716	SCV000699734	uncertain significance	not provided	2016-02-01	criteria provided, single submitter	clinical testing	Variant summary: This c.778A>G variant affects a conserved nucleotide, resulting in amino acid change from Thr to Ala. 2/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). This variant was found in 6/121390 control chromosomes at a frequency of 0.0000494, predominantly observed in African subpopulation of ExAC with MAF of 0.0002883. This frequency in African cohort exceeds the maximal expected frequency of a pathogenic allele (0.0000625) in this gene, indicating this variant is possibly a benign rare polymorphism especially in Africans. Multiple clinical labs (via ClinVar) classified this variant as VUS. The variant of interest has not been reported in affected individuals via publications, nor evaluated for functional impact by in vivo/vitro studies. Based on the currently available information, this variant has been classified as a variant of uncertain significance (VUS)-possibly benign until additional information becomes available.
Color Diagnostics, LLC DBA Color Health	RCV000160362	SCV000911045	likely benign	Hereditary cancer-predisposing syndrome	2016-03-02	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001125839	SCV001284962	likely benign	Fanconi anemia complementation group J	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000586716	SCV002046632	uncertain significance	not provided	2021-02-04	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225394	SCV002505044	uncertain significance	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000160362	SCV002529232	uncertain significance	Hereditary cancer-predisposing syndrome	2021-10-18	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002267867	SCV002551200	uncertain significance	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149846	SCV003837716	uncertain significance	Breast and/or ovarian cancer	2021-10-05	criteria provided, single submitter	clinical testing