Submissions for variant NM_000465.4(BARD1):c.733C>T (p.Gln245Ter)

dbSNP: rs587781430

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129318	SCV000184081	pathogenic	Hereditary cancer-predisposing syndrome	2023-02-15	criteria provided, single submitter	clinical testing	The p.Q245* pathogenic mutation (also known as c.733C>T), located in coding exon 4 of the BARD1 gene, results from a C to T substitution at nucleotide position 733. This changes the amino acid from a glutamine to a stop codon within coding exon 4. 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	RCV000480724	SCV000570245	pathogenic	not provided	2018-03-27	criteria provided, single submitter	clinical testing	This variant is denoted BARD1 c.733C>T at the cDNA level and p.Gln245Ter (Q245X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BARD1 Gln245Ter has been observed in at least one individual undergoing multi-gene panel testing at a clinical laboratory (LaDuca 2017). We consider this variant to be pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000129318	SCV000688210	pathogenic	Hereditary cancer-predisposing syndrome	2020-05-14	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 4 of the BARD1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in at least one individual who underwent multi-gene panel testing (PMID: 28152038). This variant has been identified in 1/213472 chromosomes 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.
Invitae	RCV000692258	SCV000820072	pathogenic	Familial cancer of breast	2023-10-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln245*) 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 present in population databases (rs587781430, gnomAD 0.001%). 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: 141005). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV000692258	SCV004044281	pathogenic	Familial cancer of breast	2023-05-19	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.