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.2336G>A (p.Arg779Gln)

CA293940

140840 (ClinVar)

Gene: CDH1

Condition: hereditary diffuse gastric adenocarcinoma

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 0339a717-77e2-4a43-8a0e-d945828d8cdb

HGVS expressions

NM_004360.5:c.2336G>A

NM_004360.5(CDH1):c.2336G>A (p.Arg779Gln)

NC_000016.10:g.68829694G>A

CM000678.2:g.68829694G>A

NC_000016.9:g.68863597G>A

CM000678.1:g.68863597G>A

NC_000016.8:g.67421098G>A

NG_008021.1:g.97403G>A

ENST00000261769.10:c.2336G>A

ENST00000261769.9:c.2336G>A

ENST00000422392.6:c.2153G>A

ENST00000562118.1:n.554G>A

ENST00000562836.5:n.2407G>A

ENST00000566510.5:c.*1002G>A

ENST00000566612.5:c.*576G>A

ENST00000611625.4:c.2399G>A

ENST00000612417.4:c.1853+3140G>A

ENST00000621016.4:c.1866-4509G>A

NM_004360.3:c.2336G>A

NM_001317184.1:c.2153G>A

NM_001317185.1:c.788G>A

NM_001317186.1:c.371G>A

NM_004360.4:c.2336G>A

NM_001317184.2:c.2153G>A

NM_001317185.2:c.788G>A

NM_001317186.2:c.371G>A

Benign

BP2_Strong BS2

BS1 PM2

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

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

CDH1 VCEP

The c.2336G>A (NM_004360.5) variant in CDH1 is a missense variant predicted to cause substitution of arginine by glutamine at amino acid 779 (p.Arg779Gln). This variant was observed in the homozygous state in an individual without a personal and/or family history of diffuse gastric cancer, lobular breast cancer (BP2_Strong; internal clinical data). This variant has been observed in more than 10 (134) individuals without a diagnosis of diffuse gastric cancer, signet ring tumor or lobular breast cancer and whose family histories do not suggest HDGC. (BS2; PMID: 29522266, 36436516; ClinVar SCVs: SCV000172951.7, SCV000288462.10, SCV000210875.16; internal lab contributors). In summary, this variant meets the criteria to be classified as benign for hereditary diffuse gastric cancer based on the ACMG/AMP criteria applied, as specified by the ClinGen CDH1 variant curation expert panel (Variant Interpretation Guidelines Version 3.1): BS2, BP2_S.

BP2_Strong

Observed in homozygous state in individual w/o dx of HDGC

BS2

This variant has been observed in more than 10 (134) individuals w/o GC, DGC, gSRC tumors, or LBC & whose families do not suggest HDGC. (BS2; PMID: 29522266, 36436516; ClinVar SCVs: SCV000172951.7, SCV000288462.10, SCV000210875.16; internal lab contributors).

BS1

The allele frequency in gnomAD v2.1.1 is 5/282,808 (0.002%).

PM2

The allele frequency in gnomAD v2.1.1 is 5/282,808 (0.002%).

Approved on: 2024-03-25

Published on: 2024-03-27

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