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.220C>T (p.Arg74Ter)

CA10583404

239891 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 8e4651fc-c286-49aa-95c4-13401d26f84a

HGVS expressions

NM_004360.4:c.220C>T
NM_004360.4(CDH1):c.220C>T (p.Arg74Ter)
NC_000016.10:g.68801726C>T
CM000678.2:g.68801726C>T
NC_000016.9:g.68835629C>T
CM000678.1:g.68835629C>T
NC_000016.8:g.67393130C>T
NG_008021.1:g.69435C>T
ENST00000261769.10:c.220C>T
ENST00000261769.9:c.220C>T
ENST00000422392.6:c.220C>T
ENST00000562836.5:n.291C>T
ENST00000564676.5:n.502C>T
ENST00000564745.1:n.215C>T
ENST00000566510.5:c.220C>T
ENST00000566612.5:c.220C>T
ENST00000611625.4:c.220C>T
ENST00000612417.4:c.220C>T
ENST00000621016.4:c.220C>T
NM_004360.3:c.220C>T
NM_001317184.1:c.220C>T
NM_001317185.1:c.-1396C>T
NM_001317186.1:c.-1600C>T
NM_004360.5:c.220C>T
NM_001317184.2:c.220C>T
NM_001317185.2:c.-1396C>T
NM_001317186.2:c.-1600C>T
NM_004360.5(CDH1):c.220C>T (p.Arg74Ter)

Pathogenic

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

Evidence Links 1

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.220C>T p.(Arg74Ter) 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). The variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; SCV000288456.3). 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
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PVS1
Predicted NMD.
PS4_Supporting
Found in one individual (76 yo) with gastric adenocarcinoma with suspected family history of gastric cancer (mother, brother), but NOT germline. SCV000288456.3 - one proband meet IGCLC HDGC criteria. - one proband does not meet IGCLC HDGC criteria. SCV000661607.2 - 3 cases do not meet HDGC criteria with unknown pathology.
Found in one individual (76 yo) with gastric adenocarcinoma with suspected family history of gastric cancer (mother, brother), but NOT germline. PubMed:25123297
PM2_Supporting
Not observed in population database.
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
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
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
PM6
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
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
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
Approved on: 2023-08-29
Published on: 2023-08-29
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