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
  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.

Variant: NM_001317186.2:c.561del

CA1139532475

981224 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: b361f4f7-29de-4a4a-99e2-94bafeac6f4f

HGVS expressions

NM_001317186.2:c.561del
NC_000016.10:g.68833376del
CM000678.2:g.68833376del
NC_000016.9:g.68867279del
CM000678.1:g.68867279del
NC_000016.8:g.67424780del
NG_008021.1:g.101085del
ENST00000261769.10:c.2526del
ENST00000261769.9:c.2526del
ENST00000422392.6:c.2343del
ENST00000562118.1:n.744del
ENST00000562836.5:n.2597del
ENST00000566510.5:c.*1192del
ENST00000566612.5:c.*766del
ENST00000611625.4:c.2589del
ENST00000612417.4:c.1854-815del
ENST00000621016.4:c.1866-827del
NM_004360.3:c.2526del
NM_001317184.1:c.2343del
NM_001317185.1:c.978del
NM_001317186.1:c.561del
NM_004360.4:c.2526del
NM_004360.5:c.2526del
NM_001317184.2:c.2343del
NM_001317185.2:c.978del
NM_004360.5(CDH1):c.2526del (p.Ala843fs)

Uncertain Significance

Met criteria codes 3
PVS1_Moderate PS4_Supporting PM2_Supporting
Not Met criteria codes 23
PS2 PS1 PS3 BA1 PP4 PP1 PP3 PP2 PM3 PM4 PM5 PM1 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.2526del (p.Ala843LeufsTer3) variant results in a premature stop codon that leads to a truncated protein. It is located within the nonsense mediated decay resistant zone, and downstream of codon 836 where the most 3' pathogenic variant in CDH1 terminates (PVS1_Moderate, PMID: 29798843). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). One family meets the HDGC criteria (PS4_Supporting; Internal lab contributor). In summary, the clinical significance of this variant is uncertain based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1_Moderate, PM2_Supporting, PS4_Supporting. This VUS variant is trending to the pathogenic side. The CDH1 VCEP will re-evaluate it, if more evidence emerge in the future.
Met criteria codes
PVS1_Moderate
PTC created in exon 16/16 at position 846 in the NMD-resistant zone, downstream of p.Glu836Ter (p.Ala843LeufsTer3)
PS4_Supporting
One family meets the HDGC criteria.
PM2_Supporting
Absent in gnomAD v2.1 & v3 in a region of sufficient coverage
Not Met criteria codes
PS2
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
BA1
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
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
PM3
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
PM5
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
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
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
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
BP5
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
Approved on: 2023-08-21
Published on: 2023-08-21
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