Submissions for variant NM_000465.4(BARD1):c.1224_1227del (p.Met408fs)

dbSNP: rs1553622164

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000569122	SCV000660908	pathogenic	Hereditary cancer-predisposing syndrome	2016-12-21	criteria provided, single submitter	clinical testing	The c.1224_1227delGTCT pathogenic mutation, located in coding exon 4 of the BARD1 gene, results from a deletion of 4 nucleotides at nucleotide positions 1224 to 1227, causing a translational frameshift with a predicted alternate stop codon (p.M408Ifs*6). 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	RCV000657366	SCV000779098	likely pathogenic	not provided	2017-08-04	criteria provided, single submitter	clinical testing	This deletion of four nucleotides in BARD1 is denoted c.1224_1227delGTCT at the cDNA level and p.Met408IlefsX6 (M408IfsX6) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TGAT[delGTCT]AGTC. The deletion causes a frameshift which changes a Methionine to an Isoleucine at codon 408, and creates a premature stop codon at position 6 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. Based on the currently available information, we consider this deletion to be a likely pathogenic variant.
Color Diagnostics, LLC DBA Color Health	RCV000569122	SCV002052464	pathogenic	Hereditary cancer-predisposing syndrome	2021-04-30	criteria provided, single submitter	clinical testing	This variant deletes 4 nucleotides 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. To our knowledge, 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 (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Myriad Genetics, Inc.	RCV003335477	SCV004044493	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.