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.1408del (p.Thr470fs)

CA645369638

428633 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: e338dcbc-38e5-47e2-bb62-ac1e7907225c
Approved on: 2023-08-25
Published on: 2023-08-25

HGVS expressions

NM_004360.5:c.1408del
NM_004360.5(CDH1):c.1408del (p.Thr470fs)
NC_000016.10:g.68815602del
CM000678.2:g.68815602del
NC_000016.9:g.68849505del
CM000678.1:g.68849505del
NC_000016.8:g.67407006del
NG_008021.1:g.83311del
ENST00000261769.10:c.1408del
ENST00000261769.9:c.1408del
ENST00000422392.6:c.1225del
ENST00000562836.5:n.1479del
ENST00000566510.5:c.*74del
ENST00000566612.5:c.1408del
ENST00000611625.4:c.1471del
ENST00000612417.4:c.1408del
ENST00000621016.4:c.1408del
NM_004360.3:c.1408del
NM_001317184.1:c.1225del
NM_001317185.1:c.-141del
NM_001317186.1:c.-412del
NM_004360.4:c.1408del
NM_001317184.2:c.1225del
NM_001317185.2:c.-141del
NM_001317186.2:c.-412del

Pathogenic

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

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.1408del (p.Thr470fs) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_Supporting; http://https://gnomad.broadinstitute.org/). The variant has been reported in a family meeting clinical criteria for HDGC (PS4_Supporting; SCV000580711.3). 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
PM2_Supporting
Variant absent from gnomAD
PVS1
Variant predicted to result in NMD with stop codon occurring at amino acid 480
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PS4_Supporting
Two gastric cancer cases in a family with one confirmed DGC (SCV000580711.3).
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
Variant absent from gnomAD
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
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
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
Variant absent from gnomAD
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
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
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
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