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.184G>A (p.Gly62Ser)

CA166005

141639 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 6119f9d6-1465-41f8-acae-c086afebdb6a

HGVS expressions

NM_004360.5:c.184G>A

NM_004360.5(CDH1):c.184G>A (p.Gly62Ser)

NC_000016.10:g.68801690G>A

CM000678.2:g.68801690G>A

NC_000016.9:g.68835593G>A

CM000678.1:g.68835593G>A

NC_000016.8:g.67393094G>A

NG_008021.1:g.69399G>A

ENST00000261769.10:c.184G>A

ENST00000261769.9:c.184G>A

ENST00000422392.6:c.184G>A

ENST00000562836.5:n.255G>A

ENST00000564676.5:n.466G>A

ENST00000564745.1:n.179G>A

ENST00000566510.5:c.184G>A

ENST00000566612.5:c.184G>A

ENST00000611625.4:c.184G>A

ENST00000612417.4:c.184G>A

ENST00000621016.4:c.184G>A

NM_004360.3:c.184G>A

NM_001317184.1:c.184G>A

NM_001317185.1:c.-1432G>A

NM_001317186.1:c.-1636G>A

NM_004360.4:c.184G>A

NM_001317184.2:c.184G>A

NM_001317185.2:c.-1432G>A

NM_001317186.2:c.-1636G>A

Likely Benign

BS2

PS1 BP7 BP3 BP4 BP1 PP4 PP3 PP2 BA1 PM2 PVS1 PM3 PM1 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 NM_004360.5(CDH1):c.184G>A (p.Gly62Ser) variant has been observed in >10 individuals without a diagnosis of diffuse gastric cancer, signet ring tumor or lobular breast cancer and whose family histories do not suggest HDGC (BS2; internal laboratory contributors). In summary, the clinical significance of this variant is classified as likely benign based on BS2 alone. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel: BS2. (CDH1 VCEP specifications version 3.1; 04/24/2023)

BS2

This variant has been observed in 166 heterozygous individuals with no diffuse gastric cancer, signet ring cell carcinoma or lobular breast cancer and/or whose family histories do not suggest HDGC (BS2; GeneDX, Ambry, Invitae). Note that this includes two individuals with personal history of unspecified gastric cancer, three individuals with personal history of lobular breast cancer and 3 individuals with family history of unspecified gastric cancer.

PS1

Not applicable

BP7

Not applicable

BP3

Not applicable

BP4

Not applicable

BP1

Not applicable

PP4

Not applicable

PP3

Not applicable

PP2

Not applicable

BA1

Allele frequency is less than 5% in ExAC, 1000 Genomes, or ESP

PM2

Allele frequency is not at extremely low frequency or absent from controls

PVS1

Not applicable

PM3

Not applicable

PM1

Not applicable

BS1

Allele frequency is not greater than expected due to disorder

Approved on: 2023-08-03

Published on: 2023-08-03

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