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]

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Variant: NM_004360.5(CDH1):c.2638G>A (p.Glu880Lys)

CA190198

184838 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 776e37b6-c807-4cd8-99c7-ad18dd7a6391

Approved on: 2023-09-25

Published on: 2023-09-27

HGVS expressions

NM_004360.5:c.2638G>A

NM_004360.5(CDH1):c.2638G>A (p.Glu880Lys)

NC_000016.10:g.68833488G>A

CM000678.2:g.68833488G>A

NC_000016.9:g.68867391G>A

CM000678.1:g.68867391G>A

NC_000016.8:g.67424892G>A

NG_008021.1:g.101197G>A

ENST00000261769.10:c.2638G>A

ENST00000261769.9:c.2638G>A

ENST00000422392.6:c.2455G>A

ENST00000562118.1:n.856G>A

ENST00000562836.5:n.2709G>A

ENST00000566510.5:c.*1304G>A

ENST00000566612.5:c.*878G>A

ENST00000611625.4:c.2701G>A

ENST00000612417.4:c.1854-703G>A

ENST00000621016.4:c.1866-715G>A

NM_004360.3:c.2638G>A

NM_001317184.1:c.2455G>A

NM_001317185.1:c.1090G>A

NM_001317186.1:c.673G>A

NM_004360.4:c.2638G>A

NM_001317184.2:c.2455G>A

NM_001317185.2:c.1090G>A

NM_001317186.2:c.673G>A

Benign

BS2 BS1

PM2 BA1

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.2638G>A (p.Glu880Lys) variant results in a missense change in the last exon of CDH1. This variant has been reported in at least five individuals meeting criteria for HDGC (PMID: 28522256, 32426482, 34537906, 32241597). However, this variant is present at a maximum frequency of 0.001153 (6 of 5,204 alleles) in the East Asian subpopulation in gnomAD, which is greater than expected for CDH1-related diffuse gastric and lobular breast cancer (BS1). This variant has also been observed in 112 individuals without DGC, LBC or SRC tumours and whose families do not suggest HDGC (BS2; internal laboratory contributors). In summary, this variant is classified as benign based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: BS1, BS2.

BS2

This variant has been reported in at least five individuals meeting IGCLC criteria for HDGC (PMID: 28522256, 32426482, 34537906, 32241597). The variant was also identified in 2 individuals with LBC under 50, and 2 individuals with a FHx of unspecified GC (internal laboratory data). However, this variant was identified in more than 112 individuals who do not meet HDGC criteria (internal laboratory data).

BS1

This variant has been observed at a maximum frequency of 0.001153 (6 of 5,204 alleles) in the East Asian subpopulation in gnomAD v3.1.2.

PM2

This variant has been observed at a maximum frequency of 0.001153 (6 of 5,204 alleles) in the East Asian subpopulation in gnomAD v3.1.2.

BA1

This variant has been observed at a maximum frequency of 0.001153 (6 of 5,204 alleles) in the East Asian subpopulation in gnomAD v3.1.2.

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