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.382delC (p.His128Ilefs)

CA496152715

486824 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: df80cd71-95e2-4ee3-b0bb-62143042f6c7

HGVS expressions

NM_004360.4:c.382delC
NM_004360.4(CDH1):c.382delC (p.His128Ilefs)
NC_000016.10:g.68801888del
CM000678.2:g.68801888del
NC_000016.9:g.68835791del
CM000678.1:g.68835791del
NC_000016.8:g.67393292del
NG_008021.1:g.69597del
ENST00000261769.10:c.382del
ENST00000261769.9:c.382del
ENST00000422392.6:c.382del
ENST00000561751.1:n.149del
ENST00000562836.5:n.453del
ENST00000564676.5:n.664del
ENST00000564745.1:n.377del
ENST00000566510.5:c.382del
ENST00000566612.5:c.382del
ENST00000611625.4:c.382del
ENST00000612417.4:c.382del
ENST00000621016.4:c.382del
NM_004360.3:c.382del
NM_001317184.1:c.382del
NM_001317185.1:c.-1234del
NM_001317186.1:c.-1438del
NM_004360.4:c.382del
NM_004360.5:c.382del
NM_001317184.2:c.382del
NM_001317185.2:c.-1234del
NM_001317186.2:c.-1438del
NM_004360.5(CDH1):c.382del (p.His128fs)

Pathogenic

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

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.382delC (p.His128Ilefs*87) 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: 15235021). 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
PVS1
p.His128IlefsTer87, predicted to undergo NMD as Premature Stop Codon (PTC) is located in Exon 5, and upstream of NMD boundary. c.382delC is in exon 3 which is not alternatively spliced, and present in all annotated Protein Coding CDH1 transcripts on Ensembl (ENST00000261769.9 [NM_004360], ENST00000422392.6 [NM_001317184, NM_001317185, NM_001317186], ENST00000611625.4, ENST00000621016.4, and ENST00000612417.4). Oliveira et al., 2009 PMID: 19269290 show LOH in tumor foci by in/del genetic profiling and no protein expression by immunohistochemistry
LOH found in tumor foci by in/del genetic profiling and no protein expression by immunohistochemistry PubMed:19269290
PS4_Supporting
Brooks-Wilson et al., 2004 PMID: 15235021. Proband with DGC at age 32, with 6 family members with gastric cancers (ages 40, 42, 45, 50, 55, 56) and 2 family members with breast cancer.
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PM2_Supporting
absent 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
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
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
PP4
Proband with DGC at age 32, with 6 family members with gastric cancers (ages 40, 42, 45, 50, 55, 56) and 2 family members with breast cancer. PubMed:15235021
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
Approved on: 2023-08-29
Published on: 2023-08-29
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