Submissions for variant NM_000465.4(BARD1):c.1023del (p.Ser342fs)

dbSNP: rs876660061

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000215348	SCV000277165	pathogenic	Hereditary cancer-predisposing syndrome	2021-04-19	criteria provided, single submitter	clinical testing	The c.1023delG pathogenic mutation, located in coding exon 4 of the BARD1 gene, results from a deletion of one nucleotide at nucleotide position 1023, causing a translational frameshift with a predicted alternate stop codon (p.S342Afs*58). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
GeneDx	RCV000480531	SCV000567414	pathogenic	not provided	2015-07-21	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in BARD1 is denoted c.1023delG at the cDNA level and p.Ser342AlafsX58 (S342AfsX58) at the protein level. The normal sequence, with the base that is deleted in braces, is TTCT[G]AGCA. The deletion causes a frameshift, which changes a Serine to an Alanine at codon 342, and creates a premature stop codon at position 58 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. we consider this variant to be pathogenic.
Invitae	RCV000800707	SCV000940437	pathogenic	Familial cancer of breast	2023-08-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser342Alafs*58) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 32427313). ClinVar contains an entry for this variant (Variation ID: 232902). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000215348	SCV001350125	pathogenic	Hereditary cancer-predisposing syndrome	2019-12-09	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 4 of the BARD1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BARD1 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.
Myriad Genetics, Inc.	RCV000800707	SCV004043290	pathogenic	Familial cancer of breast	2023-05-22	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.