ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2506G>T (p.Glu836Ter) (rs1555518239)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567031 SCV000661653 likely pathogenic Hereditary cancer-predisposing syndrome 2017-02-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting pathogenic classification,Alterations resulting in premature truncation (e.g.reading frame shift, nonsense),Confirmed de novo alteration in the setting of a new disease (appropriate phenotype) in the family
ClinGen CDH1 Variant Curation Expert Panel RCV000736285 SCV000864582 pathogenic Hereditary diffuse gastric cancer 2018-11-21 reviewed by expert panel curation The c.2506G>T (p.Glu836*) variant results in a premature stop codon that leads to a truncated protein. While it is located within the nonsense mediated decay resistance region,it is recognized as the most c-terminal pathogenic variant in CDH1 (PVS1_Strong, PMID: 29798843). This variant is absent in the gnomAD cohort (PM2; http://gnomad.broadinstitute.org). There is one known de novo observation with parental confirmation in a patient with diffuse gastric cancer and/or lobular breast cancer (PS2; PMID: 29798843). In summary, this variant meets criteria to be classified as likely pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: PVS1_Strong, PM2, PS2.

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