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.112A>C (p.Thr38Pro)

CA396452065

489846 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: eba86107-ad2f-4d6f-8e01-bb7a2412ea45

HGVS expressions

NM_004360.5:c.112A>C

NM_004360.5(CDH1):c.112A>C (p.Thr38Pro)

NC_000016.10:g.68738360A>C

CM000678.2:g.68738360A>C

NC_000016.9:g.68772263A>C

CM000678.1:g.68772263A>C

NC_000016.8:g.67329764A>C

NG_008021.1:g.6069A>C

ENST00000261769.10:c.112A>C

ENST00000261769.9:c.112A>C

ENST00000422392.6:c.112A>C

ENST00000566510.5:c.112A>C

ENST00000566612.5:c.112A>C

ENST00000611625.4:c.112A>C

ENST00000612417.4:c.112A>C

ENST00000621016.4:c.112A>C

NM_004360.3:c.112A>C

NM_001317184.1:c.112A>C

NM_001317185.1:c.-1504A>C

NM_001317186.1:c.-1708A>C

NM_004360.4:c.112A>C

NM_001317184.2:c.112A>C

NM_001317185.2:c.-1504A>C

NM_001317186.2:c.-1708A>C

Uncertain Significance

BS2_Supporting PM2_Supporting

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

Evidence Links 0

Expert Panel

CDH1 VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

CDH1 VCEP

The c.112A>C (NM_004360.5) variant in CDH1 is a missense variant predicted to cause substitution in exon 2 (p.Thr38Pro). This variant was observed in seven individuals with no DGC, LBC or SRC tumours and whose families do not suggest HDGC (BS2_Supporting; Invitae). Note that this includes two individuals with a family history of stomach cancer NOS. This variant is absent from gnomAD 2.1.1 (PM2_Spporting). In summary, this variant is classified as uncertain significance for DGLBCS based on the ACMG/AMP criteria applied, as specified by the ClinGen CDH1 VCEP: PM2_Supporting, BS2_supporting. (CDH1 VCEP specifications version 3.1; 04/24/2023)

BS2_Supporting

This variant was observed in seven individuals with no DGC, LBC or SRC tumours and whose families do not suggest HDGC (BS2_Supporting; Invitae and Ambry). Note that this includes two individuals with personal histories of endometrial cancer and colorectal cancer and family history of gastric cancer NOS.

PM2_Supporting

This variant is absent from gnomAD 2.1.1 (PM2_Supporting).

PS3

Functional studies not available for this variant.

PS2

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

PS4

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

PS1

There are no pathogenic missense variants at this position.

BA1

This variant is absent from gnomAD. Note the G allele is present in one in 156,712 alleles (0.000006381).

PP4

PP4 does not apply to CDH1.

PP1

Segregation unknown.

PP3

This variant is not predicted to alter splicing.

PP2

PP2 does not apply to CDH1.

PM3

PM3 does not apply to CDH1.

PM1

PM1 does not apply to CDH1.

PM4

PM4 does not apply to this variant.

PM5

PM5 does not apply to CDH1.

PM6

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

PVS1

PVS1 does not apply to this variant.

BS3

Functional studies not available for this variant.

BS4

Segregation unknown.

BS1

This variant is absent from gnomAD. Note the G allele is present in one in 156,712 alleles (0.000006381).

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

This variant is not predicted to alter splicing (not applied).

BP1

BP1 does not apply to CDH1.

BP5

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

BP7

BP7 does not apply to this variant.

Approved on: 2023-08-02

Published on: 2023-08-02

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