Submissions for variant NM_007294.4(BRCA1):c.5334T>C (p.Asp1778=)

gnomAD frequency: 0.00002  dbSNP: rs754152768

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165855	SCV000216604	likely benign	Hereditary cancer-predisposing syndrome	2014-09-10	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	RCV000412171	SCV000488916	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2016-07-19	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081334	SCV000560286	likely benign	Hereditary breast ovarian cancer syndrome	2025-01-12	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000165855	SCV000683299	likely benign	Hereditary cancer-predisposing syndrome	2017-05-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586029	SCV000699244	likely benign	not provided	2016-11-11	criteria provided, single submitter	clinical testing	Variant summary: The BRCA1 c.5334T>C (p.Asp1778Asp) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a damaging outcome for this substitution while 4/5 in splice prediction tools predict no impact on splicing by the variant. This variant is absent in 121004 control chromosomes. It was reported in HBOC families, however without strong evidence for causality. Furthermore, independent functional studies demonstrated the variant not to have an impact on splicing. In addition, clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000586029	SCV001470398	likely benign	not provided	2021-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000586029	SCV001895487	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30209399)
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798594	SCV002043455	likely benign	Breast and/or ovarian cancer	2019-11-26	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000165855	SCV002537844	likely benign	Hereditary cancer-predisposing syndrome	2021-01-26	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV003321533	SCV004026746	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000412171	SCV004817559	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2024-01-11	criteria provided, single submitter	clinical testing
Brotman Baty Institute, University of Washington	RCV000412171	SCV001238196	not provided	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion provided	in vitro
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000586029	SCV002034334	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000586029	SCV002035903	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004554737	SCV004774336	likely benign	BRCA1-related disorder	2019-07-22	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).