Submissions for variant NM_000465.4(BARD1):c.860_861del (p.Glu287fs)

dbSNP: rs786201868

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000164367	SCV000215002	pathogenic	Hereditary cancer-predisposing syndrome	2023-02-15	criteria provided, single submitter	clinical testing	The c.860_861delAG pathogenic mutation, located in coding exon 4 of the BARD1 gene, results from a deletion of two nucleotides at nucleotide positions 860 to 861, causing a translational frameshift with a predicted alternate stop codon (p.E287Vfs*5). This mutation has been detected in a cohort of patients who underwent multi-gene panel testing (LaDuca H et al. PLoS ONE. 2017 Feb;12:e0170843). This alteration was not detected in a cohort of 3030 pancreatic cancer patients undergoing multi-gene panel testing, but was identified in 1/123,136 gnomAD controls (Hu C et al. JAMA. 2018 06;319:2401-2409). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000703920	SCV000832847	pathogenic	Familial cancer of breast	2023-09-27	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 185015). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. This variant is present in population databases (rs786201868, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Glu287Valfs*5) in the BARD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BARD1 are known to be pathogenic (PMID: 20077502, 21344236).
Undiagnosed Diseases Network, NIH	RCV000703920	SCV002098346	likely pathogenic	Familial cancer of breast	2022-01-06	criteria provided, single submitter	clinical testing	This variant has been previously reported as disease causing in PMID: 28152038.
Myriad Genetics, Inc.	RCV000703920	SCV004045055	pathogenic	Familial cancer of breast	2023-05-19	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.