ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2324del (p.Gly775fs)

dbSNP: rs1060501248
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328351 SCV001142225 pathogenic CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-04 reviewed by expert panel curation The c.2324delG (p.Gly775Alafs) variant is predicted to result in a premature stop codon that leads to nonsense mediate decay (PVS1 and PM5_supporting). The variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). Therefore, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (CDH1 VCEP specifications version 3.1): PVS1, PM2_supporting, PM5_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV000464624 SCV000545472 pathogenic Hereditary diffuse gastric adenocarcinoma 2019-10-19 criteria provided, single submitter clinical testing Loss-of-function variants in CDH1 are known to be pathogenic (PMID: 15235021, 20373070). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 406669) This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gly775Alafs*8) in the CDH1 gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics RCV002451095 SCV002736890 pathogenic Hereditary cancer-predisposing syndrome 2014-07-24 criteria provided, single submitter clinical testing The c.2324delG pathogenic mutation, located in coding exon 15 of the CDH1 gene, results from a deletion of one nucleotide at position 2324, causing a translational frameshift with a predicted alternate stop codon. Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).

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