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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • Despite there being a valid 'cspec' property in the messages there's a discrepancy in message contents and CSPEC data: * Message Gene: CDH1 CSPEC Genes: [ 'CDH1' ] * Message MONDOs: MONDO:0100488 CSPEC MONDO: [ 'MONDO:0007648' ]
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_004360.3(CDH1):c.1009_1010delAG (p.Ser337Phefs)

CA186248

183727 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 1df1468c-5fef-4c6c-956a-e4d26dc68f5e
Approved on: 2023-08-25
Published on: 2023-08-25

HGVS expressions

NM_004360.3(CDH1):c.1009_1010delAG (p.Ser337Phefs)
NC_000016.10:g.68812135_68812136del
CM000678.2:g.68812135_68812136del
NC_000016.9:g.68846038_68846039del
CM000678.1:g.68846038_68846039del
NC_000016.8:g.67403539_67403540del
NG_008021.1:g.79844_79845del
ENST00000261769.10:c.1009_1010del
ENST00000261769.9:c.1009_1010del
ENST00000422392.6:c.1009_1010del
ENST00000561751.1:c.631_632del
ENST00000562836.5:n.1080_1081del
ENST00000565810.1:n.53_54del
ENST00000566510.5:c.853_854del
ENST00000566612.5:c.1009_1010del
ENST00000611625.4:c.1009_1010del
ENST00000612417.4:c.1009_1010del
ENST00000621016.4:c.1009_1010del
NM_004360.3:c.1009_1010del
NM_001317184.1:c.1009_1010del
NM_001317185.1:c.-607_-606del
NM_001317186.1:c.-811_-810del
NM_004360.4:c.1009_1010del
NM_004360.5:c.1009_1010del
NM_001317184.2:c.1009_1010del
NM_001317185.2:c.-607_-606del
NM_001317186.2:c.-811_-810del
More

Pathogenic

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

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.1009_1010delAG (p.Ser337Phefs) 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://https://gnomad.broadinstitute.org/). Two probands meet HDGC phenotype criteria (PS4_Moderate; SCV000212776.4). 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
PVS1
Variant predicted to undergo NMD with premature stop at position 348
PS4_Moderate
SCV000212776.4: Two probands have signet ring gastric cancer at 40s and 50s.
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PM2_Supporting
Variant is absent in gnomAD cohort
Not Met criteria codes
BA1
Variant is absent in gnomAD cohort
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
variant is predicted to result in a premature stop codon that leads to a truncated or absent protein
PP4
Use PS4 in place of PP4
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
variant is predicted to result in a premature stop codon that leads to a truncated or absent protein
PP2
variant is predicted to result in a premature stop codon that leads to a truncated or absent protein
PM3
dominant disorder
PM1
Do not use for this gene
PM4
variant is predicted to result in a premature stop codon that leads to a truncated or absent protein
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
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
Variant is absent in gnomAD cohort
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
variant is predicted to result in a premature stop codon that leads to a truncated or absent protein
BP4
variant is predicted to result in a premature stop codon that leads to a truncated or absent protein
BP1
variant is predicted to result in a premature stop codon that leads to a truncated or absent protein
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
variant is predicted to result in a premature stop codon that leads to a truncated or absent protein
Curation History
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