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_001317186.2:c.-1891T>C

CA2229914895

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 18ab9327-0d04-41eb-8f0f-9e6d70b3a2e3

HGVS expressions

NM_001317186.2:c.-1891T>C

NC_000016.10:g.68737344T>C

CM000678.2:g.68737344T>C

NC_000016.9:g.68771247T>C

CM000678.1:g.68771247T>C

NC_000016.8:g.67328748T>C

NG_008021.1:g.5053T>C

ENST00000261769.10:c.-72T>C

ENST00000261769.9:c.-72T>C

ENST00000566612.5:c.-72T>C

ENST00000611625.4:c.-72T>C

ENST00000612417.4:c.-72T>C

ENST00000621016.4:c.-72T>C

NM_004360.3:c.-72T>C

NM_001317184.1:c.-72T>C

NM_001317185.1:c.-1687T>C

NM_001317186.1:c.-1891T>C

NM_004360.4:c.-72T>C

NM_004360.5:c.-72T>C

NM_001317184.2:c.-72T>C

NM_001317185.2:c.-1687T>C

Uncertain Significance

PM2_Supporting

BA1 PVS1 BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7 PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 PM1 PM3 PM4 PM5 PM6

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.-72T>C variant occurs in the 5'UTR at a nucleotide that is not highly conserved. This variant is absent from population databases (PM2_supporting). To our knowledge, this variant has not been observed in an individual with DGC, LBC, SRC tumours or whose family history suggests HDGC. In summary, this variant meets criteria to be classified as a variant of uncertain significance based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: PM2_supporting. (CDH1 VCEP specifications version 3.1; 03/27/2023)

PM2_Supporting

This variant is absent from population databases.

BA1

This variant is absent from population databases.

PVS1

Not applicable.

BS2

This variant has not been reported.

BS4

This variant has not been reported.

BS3

Functional studies for this variant have not been reported.

BS1

This variant is absent from population databases.

BP2

This variant has not been reported in cis or trans with a pathogenic variant.

BP3

Not applicable.

BP4

BP4 is not applicable for this variant. This variant is not predicted to alter splicing and the nucleotide is not highly conserved.

BP1

Not applicable.

BP5

This variant has not been reported in a case with an alternate molecular basis for disease.

BP7

BP7 is not applicable for variants in the UTR. This variant is not predicted to alter splicing and the nucleotide is not highly conserved.

PS2

This variant has not been reported as assumed or confirmed de novo.

PS4

This variant has not been reported in individuals meeting IGCLC criteria for HDGC.

PS3

Functional studies for this variant have not been reported.

PS1

PS1 is not applicable for CDH1.

PP4

PP4 is not applicable for CDH1.

PP1

This variant has not been reported.

PP3

This variant is not predicted to alter splicing and the nucleotide is not highly conserved.

PP2

Not applicable.

PM1

PM1 is not applicable for CDH1.

PM3

PM3 is not applicable for CDH1.

PM4

Not applicable.

PM5

Pathogenic variants at the c.-72 position have not been reported. Notably, the c.-71C>G variant is classified by the CDH1 Variant Curation Expert Panel based on its frequency in the population.

PM6

This variant has not been reported as assumed or confirmed de novo.

Approved on: 2023-08-03

Published on: 2023-08-03

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