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.1612delG (p.Asp538Thrfs)

CA645509536

437928 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 47f620ff-80ee-453c-9f55-58567c1f14be
Approved on: 2023-08-25
Published on: 2023-08-25

HGVS expressions

NM_004360.4:c.1612delG
NM_004360.4(CDH1):c.1612delG (p.Asp538Thrfs)
NC_000016.10:g.68819326del
CM000678.2:g.68819326del
NC_000016.9:g.68853229del
CM000678.1:g.68853229del
NC_000016.8:g.67410730del
NG_008021.1:g.87035del
ENST00000261769.10:c.1612del
ENST00000261769.9:c.1612del
ENST00000422392.6:c.1429del
ENST00000562836.5:n.1683del
ENST00000566510.5:c.*278del
ENST00000566612.5:c.1566-2675del
ENST00000611625.4:c.1675del
ENST00000612417.4:c.1612del
ENST00000621016.4:c.1612del
NM_004360.3:c.1612del
NM_001317184.1:c.1429del
NM_001317185.1:c.64del
NM_001317186.1:c.-254-2675del
NM_004360.4:c.1612del
NM_004360.5:c.1612del
NM_001317184.2:c.1429del
NM_001317185.2:c.64del
NM_001317186.2:c.-254-2675del
NM_004360.5(CDH1):c.1612del (p.Asp538fs)
More

Pathogenic

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

Evidence Links 2

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.1612delG p.(Asp538Thrfs) 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://gnomad.broadinstitute.org). This variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; PMID: 29131691). 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
Absent in population databases.
PS4_Supporting
PMID: 29131691 - 41-year-old with metastatic GC characterized by the presence of signet ring cells.
Same patient as in PMID: 29131691 PubMed:29295527
41-year-old with metastatic GC characterized by the presence of signet ring cells PubMed:29131691
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PVS1
Exon 11 of 16. Predicted NMD.
Not Met criteria codes
BS2
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
BS4
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
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
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
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
Curation History
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