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

Variant: NM_004360.4(CDH1):c.202delT (p.Tyr68Ilefs)

CA191858

185408 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 0be29cc3-a4b0-4139-a8bf-c692422baea7

HGVS expressions

NM_004360.4:c.202delT
NM_004360.4(CDH1):c.202delT (p.Tyr68Ilefs)
NC_000016.10:g.68801708del
CM000678.2:g.68801708del
NC_000016.9:g.68835611del
CM000678.1:g.68835611del
NC_000016.8:g.67393112del
NG_008021.1:g.69417del
ENST00000261769.10:c.202del
ENST00000261769.9:c.202del
ENST00000422392.6:c.202del
ENST00000562836.5:n.273del
ENST00000564676.5:n.484del
ENST00000564745.1:n.197del
ENST00000566510.5:c.202del
ENST00000566612.5:c.202del
ENST00000611625.4:c.202del
ENST00000612417.4:c.202del
ENST00000621016.4:c.202del
NM_004360.3:c.202del
NM_001317184.1:c.202del
NM_001317185.1:c.-1414del
NM_001317186.1:c.-1618del
NM_004360.4:c.202del
NM_004360.5:c.202del
NM_001317184.2:c.202del
NM_001317185.2:c.-1414del
NM_001317186.2:c.-1618del
NM_004360.5(CDH1):c.202del (p.Tyr68fs)

Pathogenic

Met criteria codes 3
PM2_Supporting PVS1 PM5_Supporting
Not Met criteria codes 23
PP4 PP1 PP3 PP2 PM3 PM1 PM4 PM6 BA1 BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP4 BP1 PS2 PS3 PS1 PS4

Evidence Links 0

Expert Panel

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.202delT (p.Tyr68Ilefs*15) 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.
Met criteria codes
PM2_Supporting
Allele is absent from populations in gnomAD, ExAC, 1000 Genomes and ESP.
PVS1
This variant is predicted to result in a premature stop codon in exon 3 that leads to NMD.
PM5_Supporting
This variant is predicted to result in a premature stop codon in exon 3 that leads to NMD.
Not Met criteria codes
PP4
Not applicable.
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
Not applicable.
PP2
Not applicable.
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Not applicable.
PM4
Not applicable.
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
Not applicable.
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
Not applicable.
BP4
Not applicable.
BP1
Not applicable.
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
Not applicable.
PS4
This variant was reported in an individual with lobular breast cancer under 80 years and a family history of breast and liver cancer (DOI: 10.1200/PO.16.00021). This variant was also identified in many other individuals (SCV000215503.4, SCV000569632.4, SCV000812755.1). All of them do not meet IGCLC HDGC criteria.
Approved on: 2023-08-04
Published on: 2023-08-04
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