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.1636del (p.Ala546fs)

CA658658492

481028 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: e09eb7dc-fe49-4010-a553-8d846a5b2e71

HGVS expressions

NM_004360.5:c.1636del
NM_004360.5(CDH1):c.1636del (p.Ala546fs)
NC_000016.10:g.68819350del
CM000678.2:g.68819350del
NC_000016.9:g.68853253del
CM000678.1:g.68853253del
NC_000016.8:g.67410754del
NG_008021.1:g.87059del
ENST00000261769.10:c.1636del
ENST00000261769.9:c.1636del
ENST00000422392.6:c.1453del
ENST00000562836.5:n.1707del
ENST00000566510.5:c.*302del
ENST00000566612.5:c.1566-2651del
ENST00000611625.4:c.1699del
ENST00000612417.4:c.1636del
ENST00000621016.4:c.1636del
NM_004360.3:c.1636del
NM_001317184.1:c.1453del
NM_001317185.1:c.88del
NM_001317186.1:c.-254-2651del
NM_004360.4:c.1636del
NM_001317184.2:c.1453del
NM_001317185.2:c.88del
NM_001317186.2:c.-254-2651del

Pathogenic

Met criteria codes 3
PM5_Supporting PVS1 PM2_Supporting
Not Met criteria codes 23
PS1 PS3 PS2 PS4 PP3 PP2 PP4 PP1 PM4 PM1 PM3 PM6 BA1 BS3 BS4 BS1 BS2 BP7 BP5 BP3 BP4 BP1 BP2

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.1636del p.(Ala546fs) variant is predicted to result in a premature stop codon that leads to nonsense mediate decay (PVS1 and PM5_supporting). The variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). Therefore, 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 (CDH1 VCEP specifications version 3.1): PVS1, PM2_supporting, PM5_supporting.
Met criteria codes
PM5_Supporting
Exon 11 of 16. Predicted NMD.
PVS1
Exon 11 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
PS4
SCV000665113.2 (Ambry) - proband ILC in 40s, but family history does not meet criteria. Not in published studies.
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
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
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
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
Approved on: 2023-08-04
Published on: 2023-08-04
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