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]

Variant: NM_004360.4(CDH1):c.2594G>A (p.Trp865Ter)

CA396472624

496819 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: da58d938-ba22-4e68-bea6-d7a3b508312b
Approved on: 2023-08-04
Published on: 2023-08-04

HGVS expressions

NM_004360.4:c.2594G>A
NM_004360.4(CDH1):c.2594G>A (p.Trp865Ter)
NC_000016.10:g.68833444G>A
CM000678.2:g.68833444G>A
NC_000016.9:g.68867347G>A
CM000678.1:g.68867347G>A
NC_000016.8:g.67424848G>A
NG_008021.1:g.101153G>A
ENST00000261769.10:c.2594G>A
ENST00000261769.9:c.2594G>A
ENST00000422392.6:c.2411G>A
ENST00000562118.1:n.812G>A
ENST00000562836.5:n.2665G>A
ENST00000566510.5:c.*1260G>A
ENST00000566612.5:c.*834G>A
ENST00000611625.4:c.2657G>A
ENST00000612417.4:c.1854-747G>A
ENST00000621016.4:c.1866-759G>A
NM_004360.3:c.2594G>A
NM_001317184.1:c.2411G>A
NM_001317185.1:c.1046G>A
NM_001317186.1:c.629G>A
NM_004360.5:c.2594G>A
NM_001317184.2:c.2411G>A
NM_001317185.2:c.1046G>A
NM_001317186.2:c.629G>A
NM_004360.5(CDH1):c.2594G>A (p.Trp865Ter)
More

Uncertain Significance

Met criteria codes 2
PM2_Supporting PVS1_Moderate
Not Met criteria codes 24
PS1 PS3 PS2 PS4 BA1 PP3 PP2 PP4 PP1 PM5 PM4 PM1 PM3 PM6 BS3 BS4 BS1 BS2 BP7 BP5 BP3 BP4 BP1 BP2

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.2594G>A p.(Trp865Ter) variant is predicted to result in a premature stop codon that leads to a truncated protein. However, it is located within the nonsense mediated decay resistance region and is downstream of the most 3' pathogenic variant, c.2506G>T p.(Glu836Ter), PVS1_Moderate. This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (CDH1 VCEP specifications version 3.1): PVS1_Moderate, PM2_Supporting.
Met criteria codes
PM2_Supporting
Not observed in population databases.
PVS1_Moderate
Predicted to result in the loss of the last 17 aa. Downstream of most 3' pathogenic variant, p.(Glu836*).
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
PS4
Reported in the literature (Ambry Genetics lab), but the family does not meet the criteria for HGDC (van der Post et al, J Med Genet (2015) 52(6):361-74). SCV000700321.2 (one case but does not meet the HDGC criteria) and Counsyl - SCV000785524.2.
Does not meet the criteria for HDGC. PubMed:29798843
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
PM5
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
PM6
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
GeneDx- one proband (ClinGen guidelines require at least 3 individuals).
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
Curation History
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