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.105G>C (p.Glu35Asp)

CA16620230

422466 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 39819349-145e-41c0-8276-9262ba171255

Approved on: 2023-08-21

Published on: 2023-08-21

HGVS expressions

NM_004360.5:c.105G>C

NM_004360.5(CDH1):c.105G>C (p.Glu35Asp)

NC_000016.10:g.68738353G>C

CM000678.2:g.68738353G>C

NC_000016.9:g.68772256G>C

CM000678.1:g.68772256G>C

NC_000016.8:g.67329757G>C

NG_008021.1:g.6062G>C

ENST00000261769.10:c.105G>C

ENST00000261769.9:c.105G>C

ENST00000422392.6:c.105G>C

ENST00000566510.5:c.105G>C

ENST00000566612.5:c.105G>C

ENST00000611625.4:c.105G>C

ENST00000612417.4:c.105G>C

ENST00000621016.4:c.105G>C

NM_004360.3:c.105G>C

NM_001317184.1:c.105G>C

NM_001317185.1:c.-1511G>C

NM_001317186.1:c.-1715G>C

NM_004360.4:c.105G>C

NM_001317184.2:c.105G>C

NM_001317185.2:c.-1511G>C

NM_001317186.2:c.-1715G>C

Uncertain Significance

BS2_Supporting PM2_Supporting

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

Evidence Links 0

Expert Panel

CDH1 VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

CDH1 VCEP

The c.105G>C (NM_004360.5) variant in CDH1 is a missense variant predicted to predicted to cause substitution of Glu by Asp at amino acid 35 (p.Glu35Asp). This variant has been observed in more than 3 heterozygous individuals without GC, DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2_Supporting; Ambry, GeneDx, Invitae). This variant is absent from gnomAD 2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as uncertain significance for DGLBCS based on the ACMG/AMP criteria applied, as specified by the ClinGen CDH1 VCEP (CDH1 VCEP specifications version 3.1): PM2_Supporting, BS2_Supporting.

BS2_Supporting

This variant has been observed in six individuals without GC, DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2_Supporting; Ambry, GeneDx, Invitae). Note that this includes one individual with IDC with lobular features and one unaffected individual with a family history of gastric cancer.

PM2_Supporting

This variant is absent from gnomAD 2.1.1 (PM2_Supporting).

BS4

Not available.

BS3

Functional studies have not been reported for this variant.

BS1

This variant is absent from gnomAD.

BP5

To our knowledge, this variant has not been reported in a case with an alternate molecular basis for disease.

BP7

BP7 does not apply to this variant.

BP2

To our knowledge, this variant has not been reported in cis or trans with a known pathogenic variant.

BP3

BP3 does not apply to CDH1.

BP4

Multiple computational tools do not suggest that this variant impacts splicing.

BP1

BP1 does not apply to CDH1.

PVS1

PVS1 does not apply to this variant.

PS1

No other pathogenic missense variants have been reported.

PS2

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

PS4

This variant has been observed in five individuals without DGC, LBC, SRC tumours and whose families do not suggest HDGC (Ambry, GeneDx, Invitae). Note that this includes one individual with IDC with lobular features (Invitae).

PS3

Functional studies have not been reported for this variant.

BA1

This variant is absent from gnomAD.

PP4

PP4 does not apply to CDH1.

PP1

Not available.

PP3

Multiple computational tools do not suggest that this variant impacts splicing.

PP2

PP2 does not apply to CDH1.

PM5

PM5 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.

PM6

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

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