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]
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Variant: NM_004360.5(CDH1):c.2387_2406del (p.Arg796fs)

CA658798634

532446 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 1fb01c71-e29e-491f-86d2-2f85f675d043

HGVS expressions

NM_004360.5:c.2387_2406del
NM_004360.5(CDH1):c.2387_2406del (p.Arg796fs)
NC_000016.10:g.68829745_68829764del
CM000678.2:g.68829745_68829764del
NC_000016.9:g.68863648_68863667del
CM000678.1:g.68863648_68863667del
NC_000016.8:g.67421149_67421168del
NG_008021.1:g.97454_97473del
ENST00000261769.10:c.2387_2406del
ENST00000261769.9:c.2387_2406del
ENST00000422392.6:c.2204_2223del
ENST00000562118.1:n.605_624del
ENST00000562836.5:n.2458_2477del
ENST00000566510.5:c.*1053_*1072del
ENST00000566612.5:c.*627_*646del
ENST00000611625.4:c.2450_2469del
ENST00000612417.4:c.1853+3191_1853+3210del
ENST00000621016.4:c.1866-4458_1866-4439del
NM_004360.3:c.2387_2406del
NM_001317184.1:c.2204_2223del
NM_001317185.1:c.839_858del
NM_001317186.1:c.422_441del
NM_004360.4:c.2387_2406del
NM_001317184.2:c.2204_2223del
NM_001317185.2:c.839_858del
NM_001317186.2:c.422_441del

Likely Pathogenic

Met criteria codes 3
PVS1_Strong PM2_Supporting PM5_Supporting
Not Met criteria codes 23
PS1 PS3 PS2 PS4 BA1 PP3 PP2 PP1 PP4 PM4 PM1 PM3 PM6 BS2 BS3 BS4 BS1 BP3 BP4 BP1 BP2 BP7 BP5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
CDH1 VCEP
The NM_004360.5:c.2387_2406del (p.Arg796GlnfsTer4) variant in CDH1 is a frameshift variant that may cause a premature stop codon that is predicted to escape nonsense mediated decay. However, this truncated region is critical to protein function and located upstream the most 3' well-characterized pathogenic variant c.2506G>T (pGlu836Ter) (PVS1_Strong, PM5_Supporting; PMID: 29798843, ClinVar Variation ID: 479504). This variant is absent in gnomAD 2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for DGLBCS based on the ACMG/AMP criteria applied, as specified by the ClinGen CDH1 VCEP: PVS1_Strong, PM5_Supporting, PM2_Supporting. (CDH1 VCEP specifications version 3.1)
Met criteria codes
PVS1_Strong
The NM_004360.5:c.2387_2406del (p.Arg796GlnfsTer4) variant in CDH1 is a frameshift variant that may cause a premature stop codon that is predicted to escape nonsense mediated decay. However, this truncated region is critical to protein function and located upstream the most 3' well-characterized pathogenic variant c.2506G>T (pGlu836Ter)(PVS1_Strong; PMID: 29798843).
PM2_Supporting
This variant is absent in gnomAD 2.1.1 (PM2_Supporting).
PM5_Supporting
This variant is located upstream of last known pathogenic truncating variant [c.2506G>T (p.Glu836Ter)] [PMID: 29798843, ClinVar Variation ID: 479504](PM5_Supporting).
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
PS4
SCV000760787.1 (Invitae) - invasive breast with focal lobular features in 40s, family history does not meet criteria. Not in published studies.
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
PP1
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
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
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
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
Approved on: 2023-08-02
Published on: 2023-08-02
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