ClinVar Miner

Submissions for variant NM_000465.4(BARD1):c.133G>T (p.Glu45Ter)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
MGZ Medical Genetics Center RCV002289388 SCV002580889 likely pathogenic Familial cancer of breast 2022-07-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV002382507 SCV002693638 likely pathogenic Hereditary cancer-predisposing syndrome 2022-11-28 criteria provided, single submitter clinical testing The p.E45* variant (also known as c.133G>T), located in coding exon 1 of the BARD1 gene, results from a G to T substitution at nucleotide position 133. This changes the amino acid from a glutamic acid to a stop codon within coding exon 1. The predicted stop codon occurs within the first 150 nucleotides of theBARD1 gene. This alteration may escape nonsense-mediated mRNAdecay and/or be rescued by re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). However, a significant portion of the protein is affected (Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Invitae RCV002289388 SCV003239104 pathogenic Familial cancer of breast 2022-10-01 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with BARD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu45*) 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).
Myriad Genetics, Inc. RCV002289388 SCV004045212 pathogenic Familial cancer of breast 2023-05-18 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 RCV002289388 SCV004217358 likely pathogenic Familial cancer of breast 2020-12-18 criteria provided, single submitter clinical testing

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