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]

Variant: NM_004360.5(CDH1):c.1137+2T>C

Curation Version - 2.1
Curation History
JSON LD for Version 2.1

CA194301

186267 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: b74cbc6f-6e60-4c2e-a118-4341cfa4777f

Approved on: 2023-10-23

Published on: 2023-11-10

HGVS expressions

NM_004360.5:c.1137+2T>C

NM_004360.5(CDH1):c.1137+2T>C

NC_000016.10:g.68812265T>C

CM000678.2:g.68812265T>C

NC_000016.9:g.68846168T>C

CM000678.1:g.68846168T>C

NC_000016.8:g.67403669T>C

NG_008021.1:g.79974T>C

ENST00000261769.10:c.1137+2T>C

ENST00000261769.9:c.1137+2T>C

ENST00000422392.6:c.1137+2T>C

ENST00000562836.5:n.1208+2T>C

ENST00000565810.1:n.181+2T>C

ENST00000566510.5:c.981+2T>C

ENST00000566612.5:c.1137+2T>C

ENST00000611625.4:c.1137+2T>C

ENST00000612417.4:c.1137+2T>C

ENST00000621016.4:c.1137+2T>C

NM_004360.3:c.1137+2T>C

NM_001317184.1:c.1137+2T>C

NM_001317185.1:c.-479+2T>C

NM_001317186.1:c.-683+2T>C

NM_004360.4:c.1137+2T>C

NM_001317184.2:c.1137+2T>C

NM_001317185.2:c.-479+2T>C

NM_001317186.2:c.-683+2T>C

Likely Pathogenic

PM2_Supporting PS4_Supporting PVS1_Strong PM5_Supporting

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

Evidence Links 2

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

This c.1137+2T>C variant occurs at the canonical donor splice site of exon 8 (PVS1_strong, PM5_Supporting). This variant is absent from populations in gnomAD (PM2_Supporting; http://gnomad.broadinstitute.org) and has been observed in at least one individual meeting IGCLC criteria for HDGC (PS4_supporting; internal laboratory data). In summary, this variant meets criteria to be classified as likely pathogenic based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: PVS1_strong, PM2_Supporting, PS4_supporting, PM5_Supporting (Variant Interpretation Guidelines Version 3.1).

PM2_Supporting

This variant is absent from gnomAD.

PS4_Supporting

This variant was observed in an individual with DGC in 30s (Invitae). This variant has also been reported in an individual with IDC at 43 years and first-degree relative with gastric cancer of unknown histology, but whose family does not meet IGCLC criteria for HDGC (SCV000216580.4; PMID: 31296550).

PVS1_Strong

This variant occurs at the canonical splice donor site of exon 8.

PM5_Supporting

Apply PM5_Supporting to the variant with the alteration at canonical splicing site.

BA1

This variant is absent from gnomAD.

PM3

PM3 does not apply to CDH1.

PM1

PM1 does not apply to CDH1.

PM4

PM4 does not apply to this variant.

PM6

To our knowledge, this variant has not been reported as de novo.

PS2

To our knowledge, this variant has not been reported as de novo.

PS3

To our knowledge, this variant has not been assessed for splicing defects in vitro.

Abnormal splicing has been observed associated with the CDH1 c.1137+1delG allele. PubMed:31642931

Abnormal splicing has been observed associated with the CDH1 c.1137G>A allele. PubMed:15831593

PS1

PS1 does not apply to this variant.

PP4

PP4 does not apply to CDH1.

PP1

To our knowledge, segregation of this variant has not been reported.

PP3

PP3 does not apply to this variant.

PP2

PP2 does not apply to CDH1.

BS2

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

BS4

To our knowledge, segregation of this variant has not been reported.

BS3

To our knowledge, this variant has not been assessed for splicing defects in vitro.

Abnormal splicing has been observed associated with the CDH1 c.1137+1delG allele. PubMed:31642931

Abnormal splicing has been observed associated with the CDH1 c.1137G>A allele. PubMed:15831593

BS1

This variant is absent from gnomAD.

BP2

To our knowledge, this variant has not been observed in cis or trans with a pathogenic variant.

BP3

BP3 does not apply to CDH1.

BP4

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

BP1

BP1 does not apply to CDH1.

BP5

To our knowledge, this variant has not been found in a case with an alternate molecular basis for disease.

BP7

BP7 does not apply to this variant.

Curation History

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