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_004360.5(CDH1):c.1746dup (p.Leu583fs)

CA645369677

428629 (ClinVar)

Gene: CDH1 (HGNC:999)
Condition: CDH1-related diffuse gastric and lobular breast cancer (MONDO:0007648)
Inheritance Mode: Autosomal dominant inheritance
UUID: d32a3080-b708-4479-87cd-50fd1bc4f1e9
Approved on: 2023-08-04
Published on: 2023-08-04

HGVS expressions

NM_004360.5(CDH1):c.1746dup (p.Leu583fs)
NM_004360.5:c.1746dup
NC_000016.10:g.68822035dup
CM000678.2:g.68822035dup
NC_000016.9:g.68855938dup
CM000678.1:g.68855938dup
NC_000016.8:g.67413439dup
NG_008021.1:g.89744dup
ENST00000261769.10:c.1746dup
ENST00000261769.9:c.1746dup
ENST00000422392.6:c.1563dup
ENST00000562836.5:n.1817dup
ENST00000566510.5:c.*412dup
ENST00000566612.5:c.1600dup
ENST00000611625.4:c.1809dup
ENST00000612417.4:c.1746dup
ENST00000621016.4:c.1746dup
NM_004360.3:c.1746dup
NM_001317184.1:c.1563dup
NM_001317185.1:c.198dup
NM_001317186.1:c.-220dup
NM_004360.4:c.1746dup
NM_001317184.2:c.1563dup
NM_001317185.2:c.198dup
NM_001317186.2:c.-220dup
More

Pathogenic

Met criteria codes 3
PVS1 PM5_Supporting PM2_Supporting
Not Met criteria codes 23
PM4 PM1 PM3 PM6 BA1 BS2 BS3 BS4 BS1 BP7 BP5 BP3 BP4 BP1 BP2 PS1 PS3 PS2 PS4 PP3 PP2 PP4 PP1

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.1746dup p.(Leu583fs) variant is predicted to result in a premature stop codon that leads to nonsense mediate decay (PVS1 and PM5_supporting). The variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). Therefore, 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 (CDH1 VCEP specifications version 3.1): PVS1, PM2_supporting, PM5_supporting.
Met criteria codes
PVS1
Exon 12 of 16, predicted NMD.
PM5_Supporting
Exon 12 of 16, predicted NMD.
PM2_Supporting
Absent in population databases.
Not Met criteria codes
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
BA1
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
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
PS4
SCV000778897.2 (GeneDx) - 2 cases gastric cancer but no pathology. SCV000580707.3 (Ambry) - does not meet clinical criteria. PMID: 28152038 (Ambry internal data, Aliso Viejo, CA)
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
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.
ClinGen Terms of Use.
¤ Powered by BCM's Genboree.