Submissions for variant NM_000465.4(BARD1):c.365-8del

dbSNP: rs776103948

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000197210	SCV000252709	benign	Familial cancer of breast	2024-01-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000478554	SCV000564691	benign	not specified	2015-03-17	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	RCV000579971	SCV000682786	likely benign	Hereditary cancer-predisposing syndrome	2016-01-06	criteria provided, single submitter	clinical testing
Counsyl	RCV000197210	SCV000786522	likely benign	Familial cancer of breast	2018-05-17	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000478554	SCV001554515	benign	not specified	2021-03-21	criteria provided, single submitter	clinical testing	Variant summary: BARD1 c.365-8delT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8.4e-05 in 238706 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BARD1 causing Breast Cancer (8.4e-05 vs 0.00025), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.365-8delT in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Sema4, Sema4	RCV000579971	SCV002529616	likely benign	Hereditary cancer-predisposing syndrome	2021-11-01	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000197210	SCV004019267	benign	Familial cancer of breast	2023-02-24	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. 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].
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477650	SCV004222398	likely benign	not provided	2023-01-12	criteria provided, single submitter	clinical testing