Submissions for variant NM_000465.4(BARD1):c.1059C>G (p.Pro353=)

gnomAD frequency: 0.00009  dbSNP: rs368649242

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165006	SCV000215701	likely benign	Hereditary cancer-predisposing syndrome	2014-10-22	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000230501	SCV000284891	likely benign	Familial cancer of breast	2025-02-02	criteria provided, single submitter	clinical testing
Counsyl	RCV000230501	SCV000489659	likely benign	Familial cancer of breast	2016-11-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000431802	SCV000512241	benign	not specified	2015-03-27	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.
Color Diagnostics, LLC DBA Color Health	RCV000165006	SCV000537437	likely benign	Hereditary cancer-predisposing syndrome	2015-06-08	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000858607	SCV000600170	likely benign	not provided	2022-11-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000431802	SCV000918615	likely benign	not specified	2024-03-23	criteria provided, single submitter	clinical testing
Mendelics	RCV000230501	SCV001136193	likely benign	Familial cancer of breast	2019-05-28	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000165006	SCV002526976	likely benign	Hereditary cancer-predisposing syndrome	2021-02-19	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000230501	SCV004019235	benign	Familial cancer of breast	2023-02-24	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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000431802	SCV004024861	likely benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Molecular Diagnostics Laboratory, Catalan Institute of Oncology	RCV000165006	SCV005901607	likely benign	Hereditary cancer-predisposing syndrome	2024-12-19	criteria provided, single submitter	clinical testing	BP4, BP7 c.1059C>G, located in exon 4 of the BARD1 gene, is predicted to result in no splicing alteration (according to SpliceAI) and no amino acid change, p.(Pro353=) (BP4, BP7). This variant is found in 14/268102 alleles at a frequency of 0.0052% in the gnomAD v2.1.1 database, non-cancer dataset. To our knowledge, neither relevant clinical data nor well-stablished functional studies have been reported for this variant. It has been reported in the ClinVar database (2x benign,9x likely benign) and in the LOVD database (1x benign, 1x likely benign). Based on the currently available information, c.1059C>G is classified as a likely benign variant according to ACMG guidelines.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV005359494	SCV005918966	likely benign	BARD1-related cancer predisposition	2023-06-27	criteria provided, single submitter	clinical testing