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.2506G>T (p.Glu836Ter)

CA396472215

479504 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 1a5e5e0d-db23-4e6c-a7f2-002891504b0f
Approved on: 2023-08-29
Published on: 2023-08-29

HGVS expressions

NM_004360.4:c.2506G>T
NM_004360.4(CDH1):c.2506G>T (p.Glu836Ter)
NC_000016.10:g.68833356G>T
CM000678.2:g.68833356G>T
NC_000016.9:g.68867259G>T
CM000678.1:g.68867259G>T
NC_000016.8:g.67424760G>T
NG_008021.1:g.101065G>T
ENST00000261769.10:c.2506G>T
ENST00000261769.9:c.2506G>T
ENST00000422392.6:c.2323G>T
ENST00000562118.1:n.724G>T
ENST00000562836.5:n.2577G>T
ENST00000566510.5:c.*1172G>T
ENST00000566612.5:c.*746G>T
ENST00000611625.4:c.2569G>T
ENST00000612417.4:c.1854-835G>T
ENST00000621016.4:c.1866-847G>T
NM_004360.3:c.2506G>T
NM_001317184.1:c.2323G>T
NM_001317185.1:c.958G>T
NM_001317186.1:c.541G>T
NM_004360.5:c.2506G>T
NM_001317184.2:c.2323G>T
NM_001317185.2:c.958G>T
NM_001317186.2:c.541G>T
NM_004360.5(CDH1):c.2506G>T (p.Glu836Ter)

Pathogenic

Met criteria codes 3
PVS1_Strong PS2 PM2_Supporting
Not Met criteria codes 23
BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP1 BP4 PS4 PS3 PS1 PM6 PM3 PM1 PM4 PM5 PP4 PP1 PP2 PP3 BA1

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.2506G>T (p.Glu836*) variant results in a premature stop codon that leads to a truncated protein. While it is located within the nonsense mediated decay resistance region,it is recognized as the most c-terminal pathogenic variant in CDH1 (PVS1_Strong, PMID: 29798843). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). There is one known de novo observation with parental confirmation in a patient with diffuse gastric cancer and/or lobular breast cancer (PS2; 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: PVS1_Strong, PM2_Supporting, PS2.
Met criteria codes
PVS1_Strong
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
PM2_Supporting
Absent from controls in gnomAD
Not Met criteria codes
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
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
PS4
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
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
PM5
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
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
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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