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_004360.5(CDH1):c.26C>A (p.Ser9Ter)

CA396451339

651982 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 137479c7-fb2b-49f0-b469-1224ccbcb1c3

HGVS expressions

NM_004360.5:c.26C>A
NM_004360.5(CDH1):c.26C>A (p.Ser9Ter)
NC_000016.10:g.68737441C>A
CM000678.2:g.68737441C>A
NC_000016.9:g.68771344C>A
CM000678.1:g.68771344C>A
NC_000016.8:g.67328845C>A
NG_008021.1:g.5150C>A
ENST00000261769.10:c.26C>A
ENST00000261769.9:c.26C>A
ENST00000422392.6:c.26C>A
ENST00000566510.5:c.26C>A
ENST00000566612.5:c.26C>A
ENST00000611625.4:c.26C>A
ENST00000612417.4:c.26C>A
ENST00000621016.4:c.26C>A
NM_004360.3:c.26C>A
NM_001317184.1:c.26C>A
NM_001317185.1:c.-1590C>A
NM_001317186.1:c.-1794C>A
NM_004360.4:c.26C>A
NM_001317184.2:c.26C>A
NM_001317185.2:c.-1590C>A
NM_001317186.2:c.-1794C>A

Pathogenic

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

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.26C>A (p.Ser9Ter) variant is predicted to result in a premature stop codon in exon 1 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). Two families meet HDGC phenotypic criteria (PS4_moderate; SCV000947495.1 and internal contributor). 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
Loss of CDH1 function is a known mechanism of disease. This variant creates a premature translational stop signal at the codon 9 for Serin, exon 1 of the in the CDH1 gene. It is expected to result in an absent or disrupted protein product.
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PS4_Moderate
Two families meet HDGC phenotypic criteria (SCV000947495.1 and internal contributor).
PM2_Supporting
absent in gnomAD, 1000 Genomics and ESP with good coverage.
Not Met criteria codes
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
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
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
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
BA1
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
PM4
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
PM1
This variant is in the exon 1 for signal peptide.
Approved on: 2023-08-25
Published on: 2023-08-25
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