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.1488_1494delCGAGGAC (p.Glu497Leufs)

CA10580117

229907 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: f4cc2a94-3541-4121-abe1-a72e59d7a6bf
Approved on: 2023-08-25
Published on: 2023-08-25

HGVS expressions

NM_004360.4:c.1488_1494del
NM_004360.4(CDH1):c.1488_1494delCGAGGAC (p.Glu497Leufs)
NC_000016.10:g.68815682_68815688del
CM000678.2:g.68815682_68815688del
NC_000016.9:g.68849585_68849591del
CM000678.1:g.68849585_68849591del
NC_000016.8:g.67407086_67407092del
NG_008021.1:g.83391_83397del
ENST00000261769.10:c.1488_1494del
ENST00000261769.9:c.1488_1494del
ENST00000422392.6:c.1305_1311del
ENST00000562836.5:n.1559_1565del
ENST00000566510.5:c.*154_*160del
ENST00000566612.5:c.1488_1494del
ENST00000611625.4:c.1551_1557del
ENST00000612417.4:c.1488_1494del
ENST00000621016.4:c.1488_1494del
NM_004360.3:c.1488_1494del
NM_001317184.1:c.1305_1311del
NM_001317185.1:c.-61_-55del
NM_001317186.1:c.-332_-326del
NM_004360.5:c.1488_1494del
NM_001317184.2:c.1305_1311del
NM_001317185.2:c.-61_-55del
NM_001317186.2:c.-332_-326del
NM_004360.5(CDH1):c.1488_1494del (p.Glu497fs)
More

Pathogenic

Met criteria codes 4
PM2_Supporting PM5_Supporting PVS1 PS4_Supporting
Not Met criteria codes 22
PS1 PS3 PS2 PP3 PP2 PP4 PP1 PM4 PM1 PM3 PM6 BA1 BS3 BS4 BS1 BS2 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.1488_1494delCGAGGAC p.(Glu497Leufs) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is present in <1/50,000 alleles in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; PMID: 10477433). 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
gnomAD v2.1.1 - Found in 2 of 113760 alleles (0.001758%) in the non-Finnish European population. <0.002% if present in 2 or more individuals.
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PVS1
Exon 10 of 16. Predicted NMD.
PS4_Supporting
A single case of poorly differentiated, diffuse gastric cancer in an individual age 31 years (PMID: 10477433). Variant reported as 1487del7.
A single case of poorly differentiated, diffuse gastric cancer in an individual age 31 years (PMID: 10477433). Variant reported as 1487del7. PubMed:10477433
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
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
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
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
Curation History
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