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.1A>G (p.Met1Val)

CA396451176

532457 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 6d19d5b0-c34b-4794-89e5-d0173e561a83

HGVS expressions

NM_004360.5:c.1A>G
NM_004360.5(CDH1):c.1A>G (p.Met1Val)
NC_000016.10:g.68737416A>G
CM000678.2:g.68737416A>G
NC_000016.9:g.68771319A>G
CM000678.1:g.68771319A>G
NC_000016.8:g.67328820A>G
NG_008021.1:g.5125A>G
ENST00000261769.10:c.1A>G
ENST00000261769.9:c.1A>G
ENST00000422392.6:c.1A>G
ENST00000566510.5:c.1A>G
ENST00000566612.5:c.1A>G
ENST00000611625.4:c.1A>G
ENST00000612417.4:c.1A>G
ENST00000621016.4:c.1A>G
NM_004360.3:c.1A>G
NM_001317184.1:c.1A>G
NM_001317185.1:c.-1615A>G
NM_001317186.1:c.-1819A>G
NM_004360.4:c.1A>G
NM_001317184.2:c.1A>G
NM_001317185.2:c.-1615A>G
NM_001317186.2:c.-1819A>G

Pathogenic

Met criteria codes 4
PP1 PS4_Supporting PM2_Supporting PVS1
Not Met criteria codes 22
PS1 PS2 PS3 BA1 PP3 PP2 PP4 PM4 PM5 PM3 PM1 PM6 BS2 BS1 BS3 BS4 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.1A>G (p.Met1Val) 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 one proband meeting HDGC clinical criteria (PS4_supporting; SCV000760810.2). This variant was also found to co-segregate with disease in multiple affected family members (PP1; SCV000760810.2). 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_supporting, PM2_supporting, PP1.
Met criteria codes
PP1
This variant has been observed to segregate with gastric cancer in a family (SCV000760810.2).
PS4_Supporting
One proband meet HDGC phenotype criteria (SCV000760810.2).
PM2_Supporting
Absent from all population databases
PVS1
PVS1 applies to initiation codon variants
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
PM4
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
PM1
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
BS3
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
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
Approved on: 2023-08-25
Published on: 2023-08-25
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