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_004360.5(CDH1):c.2T>G (p.Met1Arg)

CA396451182

532474 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 24665ae3-8d6a-4ac8-a7b2-70d9d379c8dd

HGVS expressions

NM_004360.5:c.2T>G
NM_004360.5(CDH1):c.2T>G (p.Met1Arg)
NC_000016.10:g.68737417T>G
CM000678.2:g.68737417T>G
NC_000016.9:g.68771320T>G
CM000678.1:g.68771320T>G
NC_000016.8:g.67328821T>G
NG_008021.1:g.5126T>G
ENST00000261769.10:c.2T>G
ENST00000261769.9:c.2T>G
ENST00000422392.6:c.2T>G
ENST00000566510.5:c.2T>G
ENST00000566612.5:c.2T>G
ENST00000611625.4:c.2T>G
ENST00000612417.4:c.2T>G
ENST00000621016.4:c.2T>G
NM_004360.3:c.2T>G
NM_001317184.1:c.2T>G
NM_001317185.1:c.-1614T>G
NM_001317186.1:c.-1818T>G
NM_004360.4:c.2T>G
NM_001317184.2:c.2T>G
NM_001317185.2:c.-1614T>G
NM_001317186.2:c.-1818T>G

Pathogenic

Met criteria codes 3
PVS1 PS4_Moderate PM2_Supporting
Not Met criteria codes 23
BS1 BS4 BS3 BS2 BP7 BP5 BP3 BP4 BP1 BP2 PS1 PS2 PS3 BA1 PP3 PP2 PP4 PP1 PM6 PM4 PM1 PM5 PM3

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.2T>G (p.Met1Arg) 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 two probands/families meeting HDGC clinical criteria (PS4_Moderate; SCV000760846.2 and internal laboratory contributor). In summary, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP Variant Interpretation Guidelines Version 2 as specified by the CDH1 Variant Curation Expert Panel (v3.1): PVS1, PM2_supporting, PS4_Moderate.
Met criteria codes
PVS1
PVS1 applies to initiation codon variants
PS4_Moderate
Two probands/families meet HDGC phenotype criteria (SCV000760846.2 and internal laboratory contributor).
PM2_Supporting
Absent from all population databases
Not Met criteria codes
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
BS2
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
BP5
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
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
BP2
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
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
BA1
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
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
PM6
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
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
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2023-08-25
Published on: 2023-08-25
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