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

CA191858

185408 (ClinVar)

Gene: CDH1

Condition: hereditary diffuse gastric cancer

Inheritance Mode: Autosomal dominant inheritance

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

Approved on: 2019-04-22

Published on: 2019-09-11

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

Likely Pathogenic

• Met criteria codes: PVS1 PM2

• Not Met criteria codes: PM1 PM3 PM5 PM4 PM6 BA1 BS2 BS1 BS4 BS3 BP5 BP7 BP4 BP3 BP1 BP2 PS1 PS2 PS3 PS4 PP1 PP2 PP3 PP4

Expert Panel

Criteria Specification Information

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 a truncated or absent protein (PVS1). The variant is absent in the gnomAD cohort (PM2; http://gnomad.broadinstitute.org). This variant has been observed in multiple individuals with lobular breast cancer and other family cancer history but who do not meet HDGC clinical criteria (DOI: 10.1200/PO.16.00021, SCV000215503.4, SCV000569632.4, SCV000812755.1). In summary, this variant meets criteria to be classified as likely pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: PVS1, PM2.

Met criteria codes

• PVS1: This variant is predicted to result in a premature stop codon in exon 3 that leads to a truncated or absent protein.
• PM2: Allele is absent from populations in gnomAD, ExAC, 1000 Genomes and ESP.

Not Met criteria codes

• PM1: Not applicable.
• PM3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM5: 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
• BS2: 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
• 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
• BP5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP7: Not applicable.
• BP4: Not applicable.
• BP3: Not applicable.
• BP1: Not applicable.
• BP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS1: 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
• 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.
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP2: Not applicable.
• PP3: Not applicable.
• PP4: Not applicable.