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]
  • Gene obtained from curated document aligns with ClinVar but not with the Allele Registry data

Variant: NM_004360.4(CDH1):c.283C>T (p.Gln95Ter)

463775 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: b376ba62-95aa-49c6-8b93-54ef1ce4448e
Approved on: 2023-08-29
Published on: 2023-08-29

HGVS expressions

NM_004360.4:c.283C>T
NM_004360.4(CDH1):c.283C>T (p.Gln95Ter)
NM_004360.5(CDH1):c.283C>T (p.Gln95Ter)

Pathogenic

Met criteria codes 4
PM2_Supporting PVS1 PM5_Supporting PS4_Moderate
Not Met criteria codes 22
PP2 PP3 PP1 PP4 PM6 PM3 PM4 PM1 BA1 BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP1 BP4 PS2 PS1 PS3

Evidence Links 1

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.283C>T (p.Gln95*) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is present in <1/100,000 alleles in the gnomAD cohort. (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least 2 families meeting HDGC clinical criteria (PS4_Moderate; PMID: 17545690, internal laboratory contributor). In summary, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_Supporting, PS4_Moderate, PM5_Supporting.
Met criteria codes
PM2_Supporting
Because only 1 allele in gnomAD
PVS1
Truncation in exon 3 of 16.
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PS4_Moderate
2 families - Family 1 (Excel document). Observed in an individual with DGC at 39yo, 2 paternal aunts with GC (not known if they are carriers). Family 2: PMID: 17545690, one family with 7 GC, 2 confirmed DGC.
Table. 2. Lists family F1 with 7GC in the family 2 confirmed as DGC. Age range of GC diagnosis 39 to 76. No LBC reported. PubMed:17545690
Not Met criteria codes
PP2
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
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
Table. 2. Lists family F1 with 7GC in the family 2 confirmed as DGC. Age range of GC diagnosis 39 to 76. No LBC reported. PubMed:17545690
PM6
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
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Truncating variant. PMID: 18427545 supports PTC.
BA1
Because only 1 allele in gnomAD
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
Because only 1 allele in gnomAD
BS2
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
BP2
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
BP1
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
PS2
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
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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