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

Variant: NM_004360.5(CDH1):c.2296-2A>G

CA10580157

233417 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 432508e8-e2b3-49a8-af51-550a845af8a4

HGVS expressions

NM_004360.5:c.2296-2A>G
NM_004360.5(CDH1):c.2296-2A>G
NC_000016.10:g.68829652A>G
CM000678.2:g.68829652A>G
NC_000016.9:g.68863555A>G
CM000678.1:g.68863555A>G
NC_000016.8:g.67421056A>G
NG_008021.1:g.97361A>G
ENST00000261769.10:c.2296-2A>G
ENST00000261769.9:c.2296-2A>G
ENST00000422392.6:c.2113-2A>G
ENST00000562118.1:n.514-2A>G
ENST00000562836.5:n.2367-2A>G
ENST00000566510.5:c.*962-2A>G
ENST00000566612.5:c.*536-2A>G
ENST00000611625.4:c.2359-2A>G
ENST00000612417.4:c.1853+3098A>G
ENST00000621016.4:c.1866-4551A>G
NM_004360.3:c.2296-2A>G
NM_001317184.1:c.2113-2A>G
NM_001317185.1:c.748-2A>G
NM_001317186.1:c.331-2A>G
NM_004360.4:c.2296-2A>G
NM_001317184.2:c.2113-2A>G
NM_001317185.2:c.748-2A>G
NM_001317186.2:c.331-2A>G

Likely Pathogenic

Met criteria codes 4
PM5_Supporting PVS1_Strong PM2_Supporting PS4_Moderate
Not Met criteria codes 21
PS2 PS3 PS1 PP4 PP1 PP3 PP2 PM1 PM3 PM4 PM6 BA1 BS4 BS3 BS1 BS2 BP7 BP2 BP3 BP4 BP1

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.2296-2A>G variant is a canonical splice variant predicted to result in a truncated protein (PVS1_strong, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least two families meeting HDGC clinical criteria (PS4_moderate; SCV000760771.5). 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, PS4_moderate, PM2_supporting, PM5_Supporting.
Met criteria codes
PM5_Supporting
Apply PM5_Supporting to the variant with the alteration at canonical splicing site.
PVS1_Strong
Canonical intron 14 acceptor site variant, predicted by SpliceAI to abolish native acceptor site and create de novo acceptor site leading to 2 bp intron retention, causing a frameshift. Expected to undergo NMD.
PM2_Supporting
Absent in gnomAD v2.1.1 and v3.1 in a region of sufficient coverage
PS4_Moderate
At least 2 families that meet HDGC clinical criteria (Invitae). 5 families with insufficient data
Not Met criteria codes
PS2
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
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
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
PM4
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
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
1 individual w/o DCG, SRC tumours, or LBC & whose families do not suggest HDGC (Invitae)
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
Approved on: 2023-08-24
Published on: 2023-08-24
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.