Variant: NM_004360.5(CDH1):c.2T>C (p.Met1Thr)

CA396451185

486826 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

UUID: 3f6e0f9d-ae4a-4d07-a4a1-4f43338d71eb

Approved on: 2023-08-25

Published on: 2023-08-25

HGVS expressions

NM_004360.5:c.2T>C
NM_004360.5(CDH1):c.2T>C (p.Met1Thr)
NC_000016.10:g.68737417T>C
CM000678.2:g.68737417T>C
NC_000016.9:g.68771320T>C
CM000678.1:g.68771320T>C
NC_000016.8:g.67328821T>C
NG_008021.1:g.5126T>C
ENST00000261769.10:c.2T>C
ENST00000261769.9:c.2T>C
ENST00000422392.6:c.2T>C
ENST00000566510.5:c.2T>C
ENST00000566612.5:c.2T>C
ENST00000611625.4:c.2T>C
ENST00000612417.4:c.2T>C
ENST00000621016.4:c.2T>C
NM_004360.3:c.2T>C
NM_001317184.1:c.2T>C
NM_001317185.1:c.-1614T>C
NM_001317186.1:c.-1818T>C
NM_004360.4:c.2T>C
NM_001317184.2:c.2T>C
NM_001317185.2:c.-1614T>C
NM_001317186.2:c.-1818T>C

Pathogenic

• Met criteria codes: PS4_Moderate PM2_Supporting PVS1

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

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.2T>C (p.Met1Thr) variant alters the start codon of the CDH1 coding sequence and is predicted to lead to an absent protein (PVS1). This variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least 2 probands/families meeting HDGC clinical criteria (PS4_moderate; PMID: 20373070, SCV000760804.3). In summary, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP Variant Interpretation Guidelines Version 3.1 as specified by the CDH1 Variant Curation Expert Panel: PVS1, PS4_moderate, PM2_supporting.

Met criteria codes

• PS4_Moderate: Two probands/families meet HDGC phenotype criteria.
• PM2_Supporting: Absent from all population databases
• PVS1: PVS1 applies to initiation codon variants

Not Met criteria codes

• BS2: 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
• BP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP3: 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: 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: 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
• PP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP2: 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: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline