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.1565+1del

CA16620249

421639 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 7405419f-dadc-4d89-9f5b-981f01fc62af
Approved on: 2023-08-04
Published on: 2023-08-04

HGVS expressions

NM_004360.5:c.1565+1del
NM_004360.5(CDH1):c.1565+1del
NC_000016.10:g.68815760del
CM000678.2:g.68815760del
NC_000016.9:g.68849663del
CM000678.1:g.68849663del
NC_000016.8:g.67407164del
NG_008021.1:g.83469del
ENST00000261769.10:c.1565+1del
ENST00000261769.9:c.1565+1del
ENST00000422392.6:c.1382+1del
ENST00000562836.5:n.1636+1del
ENST00000566510.5:c.*231+1del
ENST00000566612.5:c.1565+1del
ENST00000611625.4:c.1628+1del
ENST00000612417.4:c.1565+1del
ENST00000621016.4:c.1565+1del
NM_004360.3:c.1565+1del
NM_001317184.1:c.1382+1del
NM_001317185.1:c.17+1del
NM_001317186.1:c.-255+1del
NM_004360.4:c.1565+1del
NM_001317184.2:c.1382+1del
NM_001317185.2:c.17+1del
NM_001317186.2:c.-255+1del
More

Likely Pathogenic

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

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.1565+1delG variant is a canonical splice variant predicted to result in an altered or absent protein (PVS1_strong). This variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). This variant is at +1 donor site variant with other pathogenic canonical splicing variants curated at the same splice site (PM5_supporting). In summary, this variant meets criteria to be classified as likely pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1_strong, PM2_supporting, PM5_supporting.
Met criteria codes
PVS1_Strong
Located in exon 10 canonical donor site. Possible use of cryptic splice site 6 bp downstream. No RNA studies conducted. Similar variant, c.1565+1G>T has been classified pathogenic.
PM5_Supporting
GT-AG 1,2 acceptor/donor site variant with other Pathogenic variants curated at the same splice site.
PM2_Supporting
Absent in gnomAD v2.1 & v3 in a region of sufficient coverage
Not Met criteria codes
BA1
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
BS2
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
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
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Two individuals with a family history of gastric cancer that do not fulfil HDGC clinical criteria (SCV000760795.2, SCV000570912.4)
PS3
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
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
PM6
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
PM1
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
Curation History
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