Submissions for variant NM_000465.4(BARD1):c.1325del (p.Pro442fs)

dbSNP: rs1060501287

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000461547	SCV000545583	pathogenic	Familial cancer of breast	2022-04-28	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro442Leufs*33) 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 variant has not been reported in the literature in individuals affected with BARD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 406748). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000483503	SCV000571236	likely pathogenic	not provided	2016-08-08	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in BARD1 is denoted c.1325delC at the cDNA level and p.Pro442LeufsX33 (P442LfsX33) at the protein level. The normal sequence, with the base that is deleted in braces, is ATAC[C]TTCT. The deletion causes a frameshift which changes a Proline to a Leucine at codon 442, and creates a premature stop codon at position 33 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.
Ambry Genetics	RCV002379433	SCV002691462	pathogenic	Hereditary cancer-predisposing syndrome	2022-10-27	criteria provided, single submitter	clinical testing	The c.1325delC variant, located in coding exon 5 of the BARD1 gene, results from a deletion of one nucleotide at nucleotide position 1325, causing a translational frameshift with a predicted alternate stop codon (p.P442Lfs*33). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Myriad Genetics, Inc.	RCV000461547	SCV004043480	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.