rs1555516137
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM5_SupportingPVS1PM2_Supporting
This summary comes from the ClinGen Evidence Repository: The c.1443del (p.Asn481fs) 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. LINK:https://erepo.genome.network/evrepo/ui/classification/CA658683954/MONDO:0007648/007
Frequency
Consequence
NM_004360.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.1443del | p.Asn481LysfsTer41 | frameshift_variant | 10/16 | ENST00000261769.10 | |
CDH1 | NM_001317184.2 | c.1260del | p.Asn420LysfsTer41 | frameshift_variant | 9/15 | ||
CDH1 | NM_001317185.2 | c.-106del | 5_prime_UTR_variant | 10/16 | |||
CDH1 | NM_001317186.2 | c.-377del | 5_prime_UTR_variant | 10/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH1 | ENST00000261769.10 | c.1443del | p.Asn481LysfsTer41 | frameshift_variant | 10/16 | 1 | NM_004360.5 | P1 | |
ENST00000563916.1 | n.286del | non_coding_transcript_exon_variant | 2/3 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
CDH1-related diffuse gastric and lobular breast cancer syndrome Pathogenic:1
Pathogenic, reviewed by expert panel | curation | ClinGen CDH1 Variant Curation Expert Panel | Aug 04, 2023 | The c.1443del (p.Asn481fs) 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. - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Feb 06, 2020 | This variant deletes 1 nucleotide in exon 10 of the CDH1 gene, creating a frameshift and premature translation stop signal. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of CDH1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at