Submissions for variant NM_032043.3(BRIP1):c.2893A>C (p.Arg965=)

gnomAD frequency: 0.00002  dbSNP: rs113697814

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000162637	SCV000213074	likely benign	Hereditary cancer-predisposing syndrome	2016-04-15	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.
GeneDx	RCV000300079	SCV000329165	uncertain significance	not provided	2018-07-10	criteria provided, single submitter	clinical testing	This variant is denoted BRIP1 c.2893A>C at the DNA level. This variant is silent at the coding level, preserving an Arginine at codon 965. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. In silico analyses, which include splice predictors and evolutionary conservation, are uninformative in their assessment as to whether or not the variant is damaging. BRIP1 c.2893A>C was not observed at a significant allele frequency in large population cohorts (Lek 2016). Based on currently available evidence, it is unclear whether BRIP1 c.2893A>C is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001078734	SCV000558586	likely benign	Familial cancer of breast; Fanconi anemia complementation group J	2025-01-24	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001358720	SCV001554557	likely benign	not specified	2021-03-20	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000162637	SCV002533655	likely benign	Hereditary cancer-predisposing syndrome	2021-05-06	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV004791286	SCV005406609	benign	Familial cancer of breast	2024-09-09	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.