Submissions for variant NM_000465.4(BARD1):c.1075_1095del (p.Leu359_Pro365del)

dbSNP: rs28997575

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000128959	SCV000172828	benign	Hereditary cancer-predisposing syndrome	2012-09-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000128959	SCV000172840	benign	Hereditary cancer-predisposing syndrome	2014-11-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001711296	SCV000209819	benign	not provided	2018-06-12	criteria provided, single submitter	clinical testing
Invitae	RCV000197321	SCV000252703	benign	Familial cancer of breast	2024-02-01	criteria provided, single submitter	clinical testing
Counsyl	RCV000197321	SCV000488863	benign	Familial cancer of breast	2016-07-06	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000128959	SCV000682666	benign	Hereditary cancer-predisposing syndrome	2014-11-14	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000506514	SCV000806098	benign	not specified	2016-07-19	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000197321	SCV000885061	benign	Familial cancer of breast	2023-10-27	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000506514	SCV000887577	benign	not specified	2020-07-08	criteria provided, single submitter	clinical testing
Mendelics	RCV000197321	SCV001136192	likely benign	Familial cancer of breast	2019-05-28	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000197321	SCV001440744	likely benign	Familial cancer of breast	2019-01-01	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001711296	SCV002009159	likely benign	not provided	2021-11-03	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225421	SCV002505127	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000128959	SCV002526981	benign	Hereditary cancer-predisposing syndrome	2020-10-20	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000506514	SCV002760244	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000197321	SCV004016358	benign	Familial cancer of breast	2023-07-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000197321	SCV004019237	benign	Familial cancer of breast	2023-02-24	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000506514	SCV001549936	benign	not specified		no assertion criteria provided	clinical testing	The BARD1 p.Leu359_Pro365del variant was identified in 19 of 926 proband chromosomes (frequency: 0.0205) from individuals or families with hereditary breast and ovarian cancer and was present in 4 of 140 control chromosomes (frequency: 0.03) from healthy individuals, and is reported in the literature as a polymorphism (De Brakeleer 2010, De Brakeleer 2015, Ishitobi 2003, Liu 2017, Irminger-Finger 2015). The variant was also identified in ClinVar as benign (by Ambry Genetics, GeneDx, Invitae, and Counsyl), and the Zhejiang Colon Cancer Database. The variant was not identified in Cosmic, and MutDB databases. The variant was identified in control databases in 7807 of 277012 chromosomes at a frequency of 0.03 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations at a frequency greater than 1%: South Asian (52 homozygous) in 2152 of 30774 chromosomes (freq: 0.07), East Asian (8 homozygous) in 834 of 18854 chromosomes (freq: 0.044), African (9 homozygous) in 986 of 24026 chromosomes (freq: 0.041), Latino (2 homozygous) in 1167 of 34380 chromosomes (freq: 0.034), Other in 209 of 6462 chromosomes (freq: 0.032), European (Non-Finnish) in 2254 of 126574 chromosomes (freq: 0.018), Ashkenazi Jewish in 118 of 10152 chromosomes (freq: 0.012). This variant is an in-frame deletion resulting in the removal of a 7 amino acid residues from codon 359 to 365; the impact of this alteration on BARD1 protein function is not known. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.