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.1566-1G>C

CA283310260

481704 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: aa9d80fe-4740-4b6b-99b4-743557f88750

HGVS expressions

NM_004360.5:c.1566-1G>C

NM_004360.5(CDH1):c.1566-1G>C

NC_000016.10:g.68819279G>C

CM000678.2:g.68819279G>C

NC_000016.9:g.68853182G>C

CM000678.1:g.68853182G>C

NC_000016.8:g.67410683G>C

NG_008021.1:g.86988G>C

ENST00000261769.10:c.1566-1G>C

ENST00000261769.9:c.1566-1G>C

ENST00000422392.6:c.1383-1G>C

ENST00000562836.5:n.1637-1G>C

ENST00000566510.5:c.*232-1G>C

ENST00000566612.5:c.1566-2722G>C

ENST00000611625.4:c.1629-1G>C

ENST00000612417.4:c.1566-1G>C

ENST00000621016.4:c.1566-1G>C

NM_004360.3:c.1566-1G>C

NM_001317184.1:c.1383-1G>C

NM_001317185.1:c.18-1G>C

NM_001317186.1:c.-254-2722G>C

NM_004360.4:c.1566-1G>C

NM_001317184.2:c.1383-1G>C

NM_001317185.2:c.18-1G>C

NM_001317186.2:c.-254-2722G>C

Uncertain Significance

PS4_Moderate PVS1_Moderate PM2_Supporting

PS2 PS3 PS1 BP5 BP7 BP2 BP3 BP4 BP1 PP4 PP1 PP3 PP2 BA1 PM6 PM3 PM1 PM4 PM5 BS2 BS4 BS3 BS1

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 c.1566-1G>C variant is a canonical splice variant predicted to result in the use of a cryptic splice site which preserves the reading frame (PVS1_moderate). This variant is absent in the gnomAD v2.1.1 cohort. In the gnomAD v3 it has a frequency of 0.000006978 (1 of 143,302) with a maximum non-founder allele frequency of 0.00001549 (1 of 64,570) in the European non-Finnish subpopulation (PM2_supporting; http://gnomad.broadinstitute.org). The variant has been reported in two families meeting clinical criteria for HDGC (PS4_moderate, SCV000666335.2, internal laboratory contributor). In summary, the clinical significance of this variant is classified as of uncertain significance based the ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1_moderate, PS4_moderate, PM2_supporting.

PS4_Moderate

Variant identified in two families meeting HDGC criteria

PVS1_Moderate

predicted in SpliceAI to result in the use of a cryptic splice site which preserves the reading frame

PM2_Supporting

variant is absent in gnomAD v2.1.1. Present in 1 of 64,570 alleles in the NFE subpopulation in gnomAD v3 (overall: 1 out of 143,302)

PS2