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]

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
Approved on: 2023-08-25
Published on: 2023-08-25

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
More

Pathogenic

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

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
PM2_Supporting
Absent from all population databases
PS4_Moderate
Two probands/families meet HDGC phenotype criteria (SCV000760846.2 and internal laboratory contributor).
Not Met criteria codes
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
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
PM6
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
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
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
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.