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.408A>G (p.Gln136=)

CA16614941

406639 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 79415b55-144f-49d8-8825-e503db2074df

Approved on: 2023-09-25

Published on: 2023-09-27

HGVS expressions

NM_004360.5:c.408A>G

NM_004360.5(CDH1):c.408A>G (p.Gln136=)

NC_000016.10:g.68808444A>G

CM000678.2:g.68808444A>G

NC_000016.9:g.68842347A>G

CM000678.1:g.68842347A>G

NC_000016.8:g.67399848A>G

NG_008021.1:g.76153A>G

ENST00000261769.10:c.408A>G

ENST00000261769.9:c.408A>G

ENST00000422392.6:c.408A>G

ENST00000561751.1:c.175A>G

ENST00000562836.5:n.479A>G

ENST00000564676.5:n.690A>G

ENST00000564745.1:n.403A>G

ENST00000566510.5:c.408A>G

ENST00000566612.5:c.408A>G

ENST00000611625.4:c.408A>G

ENST00000612417.4:c.408A>G

ENST00000621016.4:c.408A>G

NM_004360.3:c.408A>G

NM_001317184.1:c.408A>G

NM_001317185.1:c.-1208A>G

NM_001317186.1:c.-1412A>G

NM_004360.4:c.408A>G

NM_001317184.2:c.408A>G

NM_001317185.2:c.-1208A>G

NM_001317186.2:c.-1412A>G

Likely Benign

BS2 BP4 BP7

BA1 PP3 PM2 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 c.408A>G (p.Gln136=) variant results in a synonymous change in exon 4 of CDH1. This is a silent variant that occurs at a position that is not highly conserved and for which splicing predictors do not suggest an impact on splicing (BP4, BP7). This variant is absent from the gnomAD population database v3.1.2. This variant was identified in 29 individuals without DGC, LBC, SRC tumours and whose families do not suggest HDGC (BS2; PMID: 30287823, 36436516, and internal laboratory contributors). In summary, this variant is classified as likely benign based on ACMG/AMP criteria applied as likely benign specified by the CDH1 Variant Curation Expert Panel: BS2, BP4, BP7.

BS2

This variant was observed in 29 individuals without DGC, LBC, SRC tumours and whose families do not suggest HDGC (internal laboratory data). Please note that this variant has also been observed in one individual with ILC in 40s and an individual with unspecified GC in 40s.

BP4

No predicted splice impact: SpliceAI - delta 0.02 acceptor loss; MaxEntScan - no difference; varSEAK - class 1, no splicing effect

BP7

This is a silent variant for which in silico predictors do not suggest an impact on splicing and that occurs at a position that is not highly conserved.

BA1

This variant is absent from gnomAD v3.1.2.

PP3

This variant is not predicted to alter splicing by multiple in silico tools.

PM2

This variant is absent from gnomAD v3.1.2. However, this variant has also been identified in more than 10 individuals without DGC, LBC, SRC tumours and whose families do not suggest HDGC (BS2). Therefore, PM2_Supporting is not applied to this variant.

BS1

This variant is absent from gnomAD v3.1.2.

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