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.2446A>T (p.Lys816Ter)

CA396471960

496818 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 1c8a70db-00a5-46ce-b1a3-4a18a909c3cf
Approved on: 2024-03-25
Published on: 2024-03-27

HGVS expressions

NM_004360.5:c.2446A>T
NM_004360.5(CDH1):c.2446A>T (p.Lys816Ter)
NC_000016.10:g.68833296A>T
CM000678.2:g.68833296A>T
NC_000016.9:g.68867199A>T
CM000678.1:g.68867199A>T
NC_000016.8:g.67424700A>T
NG_008021.1:g.101005A>T
ENST00000261769.10:c.2446A>T
ENST00000261769.9:c.2446A>T
ENST00000422392.6:c.2263A>T
ENST00000562118.1:n.664A>T
ENST00000562836.5:n.2517A>T
ENST00000566510.5:c.*1112A>T
ENST00000566612.5:c.*686A>T
ENST00000611625.4:c.2509A>T
ENST00000612417.4:c.1854-895A>T
ENST00000621016.4:c.1866-907A>T
NM_004360.3:c.2446A>T
NM_001317184.1:c.2263A>T
NM_001317185.1:c.898A>T
NM_001317186.1:c.481A>T
NM_004360.4:c.2446A>T
NM_001317184.2:c.2263A>T
NM_001317185.2:c.898A>T
NM_001317186.2:c.481A>T

Likely Pathogenic

Met criteria codes 3
PM2_Supporting PS4_Supporting PVS1_Strong
Not Met criteria codes 23
BP7 BP5 BP3 BP4 BP1 BP2 PS1 PS3 PS2 PP3 PP2 PP4 PP1 PM6 PM4 PM5 PM1 PM3 BA1 BS3 BS4 BS1 BS2

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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
CDH1 VCEP
The c.2446A>T (p.Lys816Ter) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein within the NMD-resistant zone and located upstream the most 3’ well-characterized pathogenic variant c.2506G>T (p.Glu836Ter) (PVS1_Strong). The variant is absent in the gnomAD cohort (PM2_Supporting; http://https://gnomad.broadinstitute.org/). The variant has been reported in one family meeting clinical criteria for HDGC (PS4_Supporting; PMID: 29798843). In summary, this variant meets criteria to be classified as Likely Pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel(Variant Interpretation Guidelines Version 3.1): PVS1_Strong, PM2_Supporting, PS4_Supporting.
Met criteria codes
PM2_Supporting
variant not present in gnomAD database
PS4_Supporting
1 family meeting HDGC criteria
PVS1_Strong
truncation in NMD-resistant zone located upstream the most 3' well-characterized pathogenic variant c.2506G>T (p.Glu836Ter)
Not Met criteria codes
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
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
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
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
PM5
Not predicted/proved to undergo NMD.
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
BA1
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
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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