Submissions for variant NM_032043.3(BRIP1):c.2232C>T (p.Asp744=)

gnomAD frequency: 0.00006  dbSNP: rs374362388

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000212319	SCV000210849	benign	not specified	2014-07-30	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000160343	SCV000216141	likely benign	Hereditary cancer-predisposing syndrome	2014-08-18	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.
Invitae	RCV001085847	SCV000291006	benign	Familial cancer of breast; Fanconi anemia complementation group J	2024-01-29	criteria provided, single submitter	clinical testing
Counsyl	RCV000411109	SCV000490011	likely benign	Fanconi anemia complementation group J	2016-09-26	criteria provided, single submitter	clinical testing
Counsyl	RCV000411860	SCV000490012	likely benign	Neoplasm of ovary	2016-09-26	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000160343	SCV000684195	likely benign	Hereditary cancer-predisposing syndrome	2015-07-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589994	SCV000699684	benign	not provided	2016-12-09	criteria provided, single submitter	clinical testing	Variant summary: The c.2232C>T (p.Asp744=) in BRIP1 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.00009 (11/121376 chrs tested), predominantly in individuals of Latino origin (0.0004; 5/11574 chrs). The observed frequency exceeds the maximum expected allele frequency for a pathogenic variant in this gene (0.00006), suggesting that it is a benign polymorphism. The variant of interest has been cited as Benign by multiple reputable databases/clinical laboratories. Taking together, the variant was classified as Benign.
PreventionGenetics, part of Exact Sciences	RCV000589994	SCV000807128	likely benign	not provided	2017-12-20	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000589994	SCV001134012	likely benign	not provided	2022-10-25	criteria provided, single submitter	clinical testing
Mendelics	RCV000989998	SCV001140760	likely benign	Familial cancer of breast	2019-05-28	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000212319	SCV002066851	likely benign	not specified	2021-02-05	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000989998	SCV004019339	benign	Familial cancer of breast	2023-02-28	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492650	SCV004240390	likely benign	Breast and/or ovarian cancer	2023-02-23	criteria provided, single submitter	clinical testing
Leiden Open Variation Database	RCV000212319	SCV001364556	benign	not specified	2019-08-13	no assertion criteria provided	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa.