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.70G>T (p.Glu24Ter)

CA280997

12240 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
UUID: 7b7c5f44-b3d4-4d24-8272-50aaad05a175

HGVS expressions

NM_004360.4:c.70G>T
NM_004360.4(CDH1):c.70G>T (p.Glu24Ter)
NC_000016.10:g.68738318G>T
CM000678.2:g.68738318G>T
NC_000016.9:g.68772221G>T
CM000678.1:g.68772221G>T
NC_000016.8:g.67329722G>T
NG_008021.1:g.6027G>T
ENST00000261769.10:c.70G>T
ENST00000261769.9:c.70G>T
ENST00000422392.6:c.70G>T
ENST00000566510.5:c.70G>T
ENST00000566612.5:c.70G>T
ENST00000611625.4:c.70G>T
ENST00000612417.4:c.70G>T
ENST00000621016.4:c.70G>T
NM_004360.3:c.70G>T
NM_001317184.1:c.70G>T
NM_001317185.1:c.-1546G>T
NM_001317186.1:c.-1750G>T
NM_004360.5:c.70G>T
NM_001317184.2:c.70G>T
NM_001317185.2:c.-1546G>T
NM_001317186.2:c.-1750G>T
NM_004360.5(CDH1):c.70G>T (p.Glu24Ter)

Pathogenic

Met criteria codes 5
PM5_Supporting PS4_Supporting PM2_Supporting PVS1 PP1
Not Met criteria codes 21
BA1 BS3 BS4 BS1 BS2 BP7 BP5 BP3 BP4 BP1 BP2 PS1 PS3 PS2 PP3 PP2 PP4 PM4 PM1 PM3 PM6

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.70G>T p.(Glu24Ter) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). This 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; PMID: 10477433, 11104024). The variant was also found to co-segregate with disease in multiple affected family members, with 3 meioses observed (PP1; PMID: 10477433, 11104024). 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, PP1, PS4_Supporting, PM5_Supporting.
Met criteria codes
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PS4_Supporting
Found in one family with DGC (at least 3 members (siblings) affected in family 4201) [PMID: 10477433, 11104024].

PM2_Supporting
Not observed in population databases.
PVS1
Predicted NMD and upstream of the most 3' pathogenic variant c.2506G>T.
PP1
Found in one family with DGC (at least 3 members (siblings) affected) [PMID: 10477433, 11104024]. 3-4 meioises in at least one family.

Not Met criteria codes
BA1
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
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
Absent in population database
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
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
Approved on: 2023-08-29
Published on: 2023-08-29
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