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_004360.3(CDH1):c.1476_1477delAG (p.Arg492Serfs)

231528 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 03a64499-edc2-48d1-b28d-14e33704cb3d
Approved on: 2023-08-25
Published on: 2023-08-25

HGVS expressions

NM_004360.3:c.1476_1477delAG
NM_004360.3(CDH1):c.1476_1477delAG (p.Arg492Serfs)
NM_004360.5(CDH1):c.1476_1477del (p.Arg492fs)

Pathogenic

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

Evidence Links 2

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.1476_1477delAG p.(Arg492Serfs) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Moderate; PMID: 15235021, 22020549). 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
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PS4_Moderate
2 cases of DGC (32 year-old with DGC and one family member with gastric cancer; 42‐year‐old with DGC and sister, mother and grandmother with gastric cancer) (PMID: 15235021, PMID: 22020549)
32 year-old with DGC and one family member with gastric cancer. PubMed:15235021
42‐year‐old with DGC and sister, mother and grandmother with gastric cancer. PubMed:22020549
PVS1
Exon 10 of 16. Predicted NMD.
PM2_Supporting
Absent in population databases.
Not Met criteria codes
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
PS2
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
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
PM3
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
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
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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