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.60G>A (p.Trp20Ter)

CA197127

187239 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: acb398fe-3559-4b3d-8bbd-29b7dfb5b8a2
Approved on: 2023-08-29
Published on: 2023-08-29

HGVS expressions

NM_004360.4:c.60G>A
NM_004360.4(CDH1):c.60G>A (p.Trp20Ter)
NC_000016.10:g.68738308G>A
CM000678.2:g.68738308G>A
NC_000016.9:g.68772211G>A
CM000678.1:g.68772211G>A
NC_000016.8:g.67329712G>A
NG_008021.1:g.6017G>A
ENST00000261769.10:c.60G>A
ENST00000261769.9:c.60G>A
ENST00000422392.6:c.60G>A
ENST00000566510.5:c.60G>A
ENST00000566612.5:c.60G>A
ENST00000611625.4:c.60G>A
ENST00000612417.4:c.60G>A
ENST00000621016.4:c.60G>A
NM_004360.3:c.60G>A
NM_001317184.1:c.60G>A
NM_001317185.1:c.-1556G>A
NM_001317186.1:c.-1760G>A
NM_004360.5:c.60G>A
NM_001317184.2:c.60G>A
NM_001317185.2:c.-1556G>A
NM_001317186.2:c.-1760G>A
NM_004360.5(CDH1):c.60G>A (p.Trp20Ter)
More

Pathogenic

Met criteria codes 4
PM2_Supporting PVS1 PM5_Supporting PS4_Moderate
Not Met criteria codes 22
PM6 PM3 PM1 PM4 BA1 BS2 BS3 BS4 BS1 BP5 BP7 BP2 BP3 BP4 BP1 PS1 PS3 PS2 PP4 PP1 PP3 PP2

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.60G>A (p.Trp20Ter) 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 two families meeting HDGC clinical criteria (PS4_Moderate; PMID: 10072428, 28688938). 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_Moderate, PM5_Supporting.
Met criteria codes
PM2_Supporting
Not present in gnomAD
PVS1
Nonsense variant
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PS4_Moderate
Variant reported in 2 families meeting HDGC criteria
The Trp20X variant is found in one family meeting HDGC criteria, according to authors. PubMed:28688938
The Trp20X variant was present in one family where 3 individuals were affected with gastric cancer (two diagnosed under 50 years). PubMed:10072428
Not Met criteria codes
PM6
Not reported de novo
PM3
Not applicable
PM1
Not applicable
PM4
Not applicable
BA1
Not present in gnomAD
BS2
Not reported in unaffected individuals
BS3
No experiment studies published on this variant
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
Not present in gnomAD
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
Not applicable
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
Not applicable
BP4
Not applicable
BP1
Not applicable
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No experiment studies published on this variant
PS2
Not reported de novo
PP4
Not applicable
PP1
Two meioses in one family (PMID: 10072428)
PP3
Not applicable
PP2
Not applicable
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.