Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_004360.4(CDH1):c.457A>T (p.Lys153Ter)

CA396457656

569046 (ClinVar)

Gene: CDH1 (HGNC:999)

Condition: CDH1-related diffuse gastric and lobular breast cancer (MONDO:0007648)

Inheritance Mode: Autosomal dominant inheritance

UUID: a5c65338-7170-417c-941a-c6aec2c6df65

Approved on: 2023-08-04

Published on: 2023-08-04

HGVS expressions

NM_004360.4(CDH1):c.457A>T (p.Lys153Ter)

NM_004360.4:c.457A>T

NC_000016.10:g.68808493A>T

CM000678.2:g.68808493A>T

NC_000016.9:g.68842396A>T

CM000678.1:g.68842396A>T

NC_000016.8:g.67399897A>T

NG_008021.1:g.76202A>T

ENST00000261769.10:c.457A>T

ENST00000261769.9:c.457A>T

ENST00000422392.6:c.457A>T

ENST00000561751.1:c.224A>T

ENST00000562836.5:n.528A>T

ENST00000564676.5:n.739A>T

ENST00000564745.1:n.452A>T

ENST00000566510.5:c.457A>T

ENST00000566612.5:c.457A>T

ENST00000611625.4:c.457A>T

ENST00000612417.4:c.457A>T

ENST00000621016.4:c.457A>T

NM_004360.3:c.457A>T

NM_001317184.1:c.457A>T

NM_001317185.1:c.-1159A>T

NM_001317186.1:c.-1363A>T

NM_004360.5:c.457A>T

NM_001317184.2:c.457A>T

NM_001317185.2:c.-1159A>T

NM_001317186.2:c.-1363A>T

NM_004360.5(CDH1):c.457A>T (p.Lys153Ter)

Pathogenic

PM5_Supporting PVS1 PM2_Supporting

PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 BA1 BS2 BS4 BS3 BS1 PM6 PM3 PM1 PM4 BP2 BP3 BP4 BP1 BP5 BP7

Evidence Links 0

Expert Panel

CDH1 VCEP

Criteria Specification Information

Criteria Specification: ClinGen CDH1 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 3.1

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

CDH1 VCEP

The c.457A>T (p.Lys153Ter) 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.

PM5_Supporting

This variant is predicted to results in a premature stop codon in exon 4.

PVS1

This variant is predicted to results in a premature stop codon in exon 4.

PM2_Supporting

This allele is absent from populations in gnomAD, ExAC, 1000 Genomes and ESP.

PS2

To our knowledge, de novo occurrence of this variant has not been reported.

PS4

SCV000817235.1 - this family does not meet IGCLC criteria for HDGC.

PS3

PS3 applies only to splicing variants.

PS1

PS1 does not apply to CDH1.

PP4

PP4 does not apply to CDH1.

PP1

To our knowledge, segregation of this variant has not been reported.

PP3

PP3 does not apply to nonsense variants.

PP2

PP2 does not apply to CDH1.

BA1

This allele is absent from populations in gnomAD, ExAC, 1000 Genomes and ESP.

BS2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS4

To our knowledge, segregation of this variant has not been reported.

BS3

BS3 applies only to splicing variants.

BS1

This allele is absent from populations in gnomAD, ExAC, 1000 Genomes and ESP.

PM6

To our knowledge, de novo occurrence of this variant has not been reported.

PM3

To our knowledge, this variant has not been reported in cis or trans with a pathogenic variant.

PM1

PM1 does not apply to CDH1.

PM4

PM4 does not apply to nonsense variants

BP2

To our knowledge, this variant has not been reported in cis or trans with a pathogenic variant.

BP3

BP3 does not apply to CDH1.

BP4

BP4 does not apply to nonsense variants.

BP1

BP1 does not apply to CDH1.

BP5

To our knowledge, this variant has not been reported in a case with an alternate molecular basis for disease.

BP7

BP7 does not apply to nonsense variants.

Curation History

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