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.504delA (p.Gly169Alafs)

CA348941

220776 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 47cfd75c-4c6e-4e49-a686-94e05a7c43db

HGVS expressions

NM_004360.4:c.504del
NM_004360.4(CDH1):c.504delA (p.Gly169Alafs)
NC_000016.10:g.68808540del
CM000678.2:g.68808540del
NC_000016.9:g.68842443del
CM000678.1:g.68842443del
NC_000016.8:g.67399944del
NG_008021.1:g.76249del
ENST00000261769.10:c.504del
ENST00000261769.9:c.504del
ENST00000422392.6:c.504del
ENST00000561751.1:n.271del
ENST00000562836.5:n.575del
ENST00000564676.5:n.786del
ENST00000564745.1:n.499del
ENST00000566510.5:c.504del
ENST00000566612.5:c.504del
ENST00000567320.1:n.14del
ENST00000611625.4:c.504del
ENST00000612417.4:c.504del
ENST00000621016.4:c.504del
NM_004360.3:c.504del
NM_001317184.1:c.504del
NM_001317185.1:c.-1112del
NM_001317186.1:c.-1316del
NM_004360.5:c.504del
NM_001317184.2:c.504del
NM_001317185.2:c.-1112del
NM_001317186.2:c.-1316del
NM_004360.5(CDH1):c.504del (p.Gly169fs)

Pathogenic

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

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.504delA p.(Gly169Alafs) 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; DOI: 10.1200/PO.16.00021). 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
PS4_Supporting
DOI: 10.1200/PO.16.00021 (Lowstuter et al, JCO Precision Oncology - published online March 29, 2017) - one 44yo individual with ILC (initial path: ductal but re-classified to lobular due to absence of CDH1 expression in tumour). Reported to fulfill the IGCLC criteria (2010 and 2015). 4 family members with gastric cancer (no pathology provided).
PM2_Supporting
Absent in population databases.
PVS1
Exon 4 of 16. Predicted NMD.
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo 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
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
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
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
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
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
Approved on: 2023-08-25
Published on: 2023-08-25
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