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

UUID: 0be29cc3-a4b0-4139-a8bf-c692422baea7

Approved on: 2023-08-04

Published on: 2023-08-04

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: PVS1 PM5_Supporting PM2_Supporting

• Not Met criteria codes: PP4 PP1 PP3 PP2 PM6 PM3 PM1 PM4 BS4 BS3 BS1 BS2 BP2 BP3 BP4 BP1 BP5 BP7 BA1 PS2 PS3 PS1 PS4

Expert Panel

CDH1 VCEP

Criteria Specification Information

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

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

• 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.
• PM2_Supporting: Allele is absent from populations in gnomAD, ExAC, 1000 Genomes and ESP.

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.
• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• 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.
• 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
• 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.
• BP5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP7: Not applicable.
• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• 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.