Evidence Repository - Clinical Genome Resources

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.833-9C>G

CA10583413

239915 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 7e1429df-b9e4-4ba3-810e-c19d3cc64d4d

Approved on: 2023-08-28

Published on: 2023-09-27

HGVS expressions

NM_004360.5:c.833-9C>G

NM_004360.5(CDH1):c.833-9C>G

NC_000016.10:g.68811675C>G

CM000678.2:g.68811675C>G

NC_000016.9:g.68845578C>G

CM000678.1:g.68845578C>G

NC_000016.8:g.67403079C>G

NG_008021.1:g.79384C>G

ENST00000261769.10:c.833-9C>G

ENST00000261769.9:c.833-9C>G

ENST00000422392.6:c.833-9C>G

ENST00000561751.1:c.455-9C>G

ENST00000562836.5:n.904-9C>G

ENST00000566510.5:c.677-9C>G

ENST00000566612.5:c.833-9C>G

ENST00000611625.4:c.833-9C>G

ENST00000612417.4:c.833-9C>G

ENST00000621016.4:c.833-9C>G

NM_004360.3:c.833-9C>G

NM_001317184.1:c.833-9C>G

NM_001317185.1:c.-783-9C>G

NM_001317186.1:c.-987-9C>G

NM_004360.4:c.833-9C>G

NM_001317184.2:c.833-9C>G

NM_001317185.2:c.-783-9C>G

NM_001317186.2:c.-987-9C>G

Likely Pathogenic

PS4_Moderate PP3 PM2_Supporting PS3

PVS1 BA1 BP7 BP3 BP4 BP1 BS2 BS3 BS1 PP4 PP2 PS1 PM3 PM1

Evidence Links 0

Expert Panel

CDH1 VCEP

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 NM_004360.5(CDH1):c.833-9C>G variant is an intronic variant in the vicinity of the 3' splice site of intron 6. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). There are at least 3 in silico predictors in agreement that this variant affects splicing (PP3). Additionally, this variant has been reported in at least two families meeting HDGC clinical criteria (PS4_Moderate; internal laboratory contributor). Furthermore, RNA analysis has demonstrated a novel eight base pair insertion (TCTTCCAG) resulting in a premature stop codon (p.G278Vfs*7) (PS3, internal data). In summary, this variant is classified as likely pathogenic based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PS3, PS4_supporting, PM2_supporting, PP3.

PS4_Moderate

Two families meet HDGC criteria (Ambry, Invitae).

PP3

The results from three in silico predictors, SpliceAI, MaxEntScan and NetGene2, predict a damaging effect on CDH1 function (PP3).

PM2_Supporting

The NM_004360.5(CDH1):c.833-9C>G is not present in population databases.

PS3

RNA studies showed r.832_833ins833-8_833-1 p.G278Vfs*7 associated with this variant (Ambry).

PVS1

Th NM_004360.5(CDH1):c.833-9C>G variant is an intronic variant.

BA1

The NM_004360.5(CDH1):c.833-9C>G is not present in population databases.

BP7

The NM_004360.5(CDH1):c.833-9C>G variant is an intronic variant.

BP3

Not applicable for CDH1.

BP4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BP1

Not applicable for CDH1.

BS2

One family does not meet HDGC criteria.

BS3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS1

The NM_004360.5(CDH1):c.833-9C>G is not present in population databases.

PP4

Not applicable for CDH1.

PP2

Not applicable for CDH1.

PS1

Not applicable for CDH1.

PM3

Not applicable for CDH1.

PM1

Not applicable for CDH1.

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.