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.2100del (p.Val701Serfs)

CA658683961

492677 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 71001505-c352-40be-b876-0a9c4bd2ef36
Approved on: 2023-08-29
Published on: 2023-08-29

HGVS expressions

NM_004360.4:c.2100del
NM_004360.4(CDH1):c.2100del (p.Val701Serfs)
NC_000016.10:g.68823562del
CM000678.2:g.68823562del
NC_000016.9:g.68857465del
CM000678.1:g.68857465del
NC_000016.8:g.67414966del
NG_008021.1:g.91271del
ENST00000261769.10:c.2100del
ENST00000261769.9:c.2100del
ENST00000422392.6:c.1917del
ENST00000562118.1:n.318del
ENST00000562836.5:n.2171del
ENST00000566510.5:c.*766del
ENST00000566612.5:c.*340del
ENST00000611625.4:c.2163del
ENST00000612417.4:c.1830+1443del
ENST00000621016.4:c.1865+1408del
NM_004360.3:c.2100del
NM_001317184.1:c.1917del
NM_001317185.1:c.552del
NM_001317186.1:c.135del
NM_004360.5:c.2100del
NM_001317184.2:c.1917del
NM_001317185.2:c.552del
NM_001317186.2:c.135del
NM_004360.5(CDH1):c.2100del (p.Val701fs)
More

Pathogenic

Met criteria codes 4
PM2_Supporting PS4_Supporting PVS1 PM5_Supporting
Not Met criteria codes 22
PS1 PS3 PS2 PP3 PP2 PP4 PP1 BA1 PM4 PM1 PM3 PM6 BS2 BS3 BS4 BS1 BP7 BP5 BP3 BP4 BP1 BP2

Evidence Links 1

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.2100del p.(Val701Serfs) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; PMID: 26182300). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). 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_Supporting, PM5_Supporting.
Met criteria codes
PM2_Supporting
Not observed in population databases.
PS4_Supporting
Identified in one family with diffuse gastric cancer (proband diagnosed at 20 yo, at least 2 DGC cases in the family).
Identified in one family with diffuse gastric cancer (proband diagnosed 20 yo, at least 2 DGC cases in the family). PubMed:26182300
PVS1
Upstream of codon 795, which is the NMD boundary.
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
Not Met criteria codes
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
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
BA1
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
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
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
Curation History
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