rs1555516545
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM5_SupportingPVS1PM2_SupportingPS4_Supporting
This summary comes from the ClinGen Evidence Repository: The c.1612delG p.(Asp538Thrfs) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; PMID:29131691). In summary, 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 (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_Supporting, PS4_Supporting, PM5_Supporting. LINK:https://erepo.genome.network/evrepo/ui/classification/CA645509536/MONDO:0007648/007
Frequency
Consequence
NM_004360.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.1612delG | p.Asp538fs | frameshift_variant | 11/16 | ENST00000261769.10 | NP_004351.1 | |
CDH1 | NM_001317184.2 | c.1429delG | p.Asp477fs | frameshift_variant | 10/15 | NP_001304113.1 | ||
CDH1 | NM_001317185.2 | c.64delG | p.Asp22fs | frameshift_variant | 11/16 | NP_001304114.1 | ||
CDH1 | NM_001317186.2 | c.-254-2675delG | intron_variant | NP_001304115.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDH1 | ENST00000261769.10 | c.1612delG | p.Asp538fs | frameshift_variant | 11/16 | 1 | NM_004360.5 | ENSP00000261769.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary diffuse gastric adenocarcinoma Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto | Aug 01, 2022 | PVS1; PS4_Supporting; PM2 (PMID: 30311375) - |
Pathogenic, criteria provided, single submitter | research | Immunopatologia e Biomarcatori Oncologici/Bio-proteomics facility, Centro di Riferimento Oncologico | Jan 02, 2017 | age<50 years, diffuse type, male, clinical aggressive form - |
CDH1-related diffuse gastric and lobular breast cancer syndrome Pathogenic:1
Pathogenic, reviewed by expert panel | curation | ClinGen CDH1 Variant Curation Expert Panel | Aug 25, 2023 | The c.1612delG p.(Asp538Thrfs) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; PMID: 29131691). In summary, 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 (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_Supporting, PS4_Supporting, PM5_Supporting. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at