Submissions for variant NM_000465.4(BARD1):c.1438T>C (p.Leu480=)

dbSNP: rs786203220

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000166437	SCV000217232	likely benign	Hereditary cancer-predisposing syndrome	2014-11-06	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.
Color Diagnostics, LLC DBA Color Health	RCV000166437	SCV001342351	likely benign	Hereditary cancer-predisposing syndrome	2019-03-04	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001280608	SCV001467822	likely benign	not specified	2020-12-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002053986	SCV002453209	likely benign	Familial cancer of breast	2024-10-20	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000166437	SCV002527008	likely benign	Hereditary cancer-predisposing syndrome	2021-07-27	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV002053986	SCV005406362	benign	Familial cancer of breast	2024-07-25	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.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001358030	SCV001553662	likely benign	Familial ovarian cancer		no assertion criteria provided	clinical testing	The BARD1 p.Leu480= variant was not identified in the literature nor was it identified in the Cosmic, or Zhejiang University databases. The variant was identified in dbSNP (ID: rs786203220) as "With Likely benign allele", and in ClinVar (classified as likely benign by Ambry Genetics). The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Leu480= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, 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 the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.