Submissions for variant NM_000465.4(BARD1):c.773T>C (p.Ile258Thr)

gnomAD frequency: 0.00004  dbSNP: rs146223579

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129102	SCV000183813	likely benign	Hereditary cancer-predisposing syndrome	2019-03-14	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	RCV000203950	SCV000259704	benign	Familial cancer of breast	2025-01-23	criteria provided, single submitter	clinical testing
GeneDx	RCV000588107	SCV000524729	likely benign	not provided	2020-09-18	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26315354, 27978560, 23056176, 30925164)
Color Diagnostics, LLC DBA Color Health	RCV000129102	SCV000682815	benign	Hereditary cancer-predisposing syndrome	2016-05-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588107	SCV000696789	benign	not provided	2016-02-01	criteria provided, single submitter	clinical testing	Variant summary: BARD1 c.773T>C variant affects a non-conserved nucleotide, resulting in amino acid change from Ile to Thr. 3/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). This variant is found in 80/122240 control chromosomes (1 homozygote) at a frequency of 0.0006545, which is about 3 times of maximal expected frequency of a pathogenic allele (0.0002188); and the variant is 26 fold higher in South Asians, highly suggesting this variant is a benign polymorphism found in South Asians. Additionally, at least one diagnostic clinical lab has classified this variant as likely benign. Taken together, this variant was classified as benign.
Counsyl	RCV000203950	SCV000784929	uncertain significance	Familial cancer of breast	2017-02-06	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000588107	SCV000888812	benign	not provided	2018-02-19	criteria provided, single submitter	clinical testing
Cancer Genomics Group, Japanese Foundation For Cancer Research	RCV001030670	SCV001193498	uncertain significance	Hereditary breast ovarian cancer syndrome	2022-03-30	criteria provided, single submitter	research
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV001030670	SCV002505131	likely benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000129102	SCV002529653	benign	Hereditary cancer-predisposing syndrome	2021-03-01	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000203950	SCV004019272	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].