Submissions for variant NM_000465.4(BARD1):c.55G>T (p.Glu19Ter)

dbSNP: rs752514155

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000215389	SCV000277998	pathogenic	Hereditary cancer-predisposing syndrome	2021-07-15	criteria provided, single submitter	clinical testing	The p.E19* pathogenic mutation (also known as c.55G>T), located in coding exon 1 of the BARD1 gene, results from a G to T substitution at nucleotide position 55. This changes the amino acid from a glutamic acid to a stop codon within coding exon 1. 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.
Invitae	RCV000458694	SCV000545608	pathogenic	Familial cancer of breast	2024-01-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu19*) 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 (rs752514155, gnomAD 0.02%). 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: 233594). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000482172	SCV000567257	pathogenic	not provided	2015-07-10	criteria provided, single submitter	clinical testing	This pathogenic variant is denoted BARD1 c.55G>T at the cDNA level and p.Glu19Ter (E19X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamic Acid to a premature stop codon (GAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000215389	SCV000682796	pathogenic	Hereditary cancer-predisposing syndrome	2021-06-03	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 1 of the BARD1 gene, creating a 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 been identified in 7/247256 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000482172	SCV000887597	pathogenic	not provided	2017-11-27	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000458694	SCV000914897	likely pathogenic	Familial cancer of breast	2024-04-24	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000458694	SCV001361542	likely pathogenic	Familial cancer of breast	2019-07-10	criteria provided, single submitter	clinical testing	Variant summary: BARD1 c.55G>T (p.Glu19X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2.8e-05 in 215878 control chromosomes. To our knowledge, no occurrence of c.55G>T in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. At-least one co-occurrence with other pathogenic variant has been reported (BRCA1 c.45delT, p.Asn16MetfsX7) at our laboratory. Six clinical diagnostic laboratories (Pathogenic n=5; VUS n=1) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Myriad Genetics, Inc.	RCV000458694	SCV004044201	pathogenic	Familial cancer of breast	2023-05-17	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.
Baylor Genetics	RCV000458694	SCV004217175	likely pathogenic	Familial cancer of breast	2023-09-02	criteria provided, single submitter	clinical testing