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.360dup (p.His121fs)

CA10583408

239903 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e116f274-4c06-47a0-a9a0-fef88440fff9

HGVS expressions

NM_004360.5:c.360dup

NM_004360.5(CDH1):c.360dup (p.His121fs)

NC_000016.10:g.68801866dup

CM000678.2:g.68801866dup

NC_000016.9:g.68835769dup

CM000678.1:g.68835769dup

NC_000016.8:g.67393270dup

NG_008021.1:g.69575dup

ENST00000261769.10:c.360dup

ENST00000261769.9:c.360dup

ENST00000422392.6:c.360dup

ENST00000561751.1:n.127dup

ENST00000562836.5:n.431dup

ENST00000564676.5:n.642dup

ENST00000564745.1:n.355dup

ENST00000566510.5:c.360dup

ENST00000566612.5:c.360dup

ENST00000611625.4:c.360dup

ENST00000612417.4:c.360dup

ENST00000621016.4:c.360dup

NM_004360.3:c.360dup

NM_001317184.1:c.360dup

NM_001317185.1:c.-1256dup

NM_001317186.1:c.-1460dup

NM_004360.4:c.360dup

NM_001317184.2:c.360dup

NM_001317185.2:c.-1256dup

NM_001317186.2:c.-1460dup

Pathogenic

PVS1 PS4_Supporting PM2_Supporting PM5_Supporting

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

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.360dupG (p.His121Alafs*47) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting, SCV000288479.2). In summary, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_Supporting, PS4_Supporting, PM5_Supporting.

PVS1

This variant occurs in exon 3 and is predicted to result in a premature stop codon that leads to a truncated or absent protein.

PS4_Supporting

This variant was identified in a proband meeting the HDGC criteria (SCV000288479.2).

PM2_Supporting

This variant is absent from populations in gnomAD, ExAC, 1000 Genomes and ESP.

PM5_Supporting

Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.

PM3

PM3 does not apply to CDH1.

PM1

PM1 does not apply to CDH1.

PM4

PM4 does not apply to frameshift variants.

PS2

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

PS3

PS3 does not apply to frameshift variants.

PS1

PS1 does not apply to this variant.

PM6

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

BA1

This variant is absent from populations in gnomAD, ExAC, 1000 Genomes and ESP.

BP2

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

BP3

BP3 does not apply to CDH1.

BP4

BP4 does not apply to frameshift variants.

BP1

BP1 does not apply to CDH1.

BP5

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

BP7

BP7 does not apply to frameshift variants.

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

BS3 does not apply to frameshift variants.

BS1

This variant is absent from populations in gnomAD, ExAC, 1000 Genomes and ESP.

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 frameshift variants.

PP2

PP2 does not apply to CDH1.

Approved on: 2023-08-25

Published on: 2023-08-25

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