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_004360.4(CDH1):c.1023T>G (p.Tyr341Ter)

CA281453

156374 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 36f417ce-8eb5-453a-99cc-96c68913737f

HGVS expressions

NM_004360.4:c.1023T>G
NM_004360.4(CDH1):c.1023T>G (p.Tyr341Ter)
NC_000016.10:g.68812149T>G
CM000678.2:g.68812149T>G
NC_000016.9:g.68846052T>G
CM000678.1:g.68846052T>G
NC_000016.8:g.67403553T>G
NG_008021.1:g.79858T>G
ENST00000261769.10:c.1023T>G
ENST00000261769.9:c.1023T>G
ENST00000422392.6:c.1023T>G
ENST00000561751.1:n.645T>G
ENST00000562836.5:n.1094T>G
ENST00000565810.1:n.67T>G
ENST00000566510.5:c.867T>G
ENST00000566612.5:c.1023T>G
ENST00000611625.4:c.1023T>G
ENST00000612417.4:c.1023T>G
ENST00000621016.4:c.1023T>G
NM_004360.3:c.1023T>G
NM_001317184.1:c.1023T>G
NM_001317185.1:c.-593T>G
NM_001317186.1:c.-797T>G
NM_004360.5:c.1023T>G
NM_001317184.2:c.1023T>G
NM_001317185.2:c.-593T>G
NM_001317186.2:c.-797T>G
NM_004360.5(CDH1):c.1023T>G (p.Tyr341Ter)

Pathogenic

Met criteria codes 4
PVS1 PS4_Supporting PM2_Supporting PM5_Supporting
Not Met criteria codes 22
BP2 BP3 BP4 BP1 BP5 BP7 PS2 PS3 PS1 BA1 PP4 PP1 PP3 PP2 PM6 PM3 PM1 PM4 BS2 BS4 BS3 BS1

Evidence Links 5

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.1023T>G (p.Tyr341*) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). The variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; PMID: 27192129). 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_Supporting, PM5_Supporting.
Met criteria codes
PVS1
Introduction of a PTC at codon 341 in exon 8 of 16. Predicted to undergo NMD
PS4_Supporting
One Northern Brazilian family that fulfils the clinical criteria for HDGC (PMID: 27192129)
Review article that references the presence of the variant in two other studies (Guliford et al & El-Husny et al) PubMed:29511593
One Northern Brazilian family that fulfils the clinical criteria for HDGC of the International Gastric Cancer Linkage Consortium. Case1 and case 3 are siblings and both carriers (1 meiosis). PubMed:27192129
Review article. Only information about the variant is that it is unpublished results from University of Otago. PubMed:20373070
References the proband from Guilford et al 2010 PubMed:22225527
Review article in German PubMed:20824432
PM2_Supporting
Absent in gnomAD
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
Not Met criteria codes
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
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
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
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
PS1
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
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
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
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
PM1
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
BS2
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
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2023-08-29
Published on: 2023-08-29
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