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.92G>T (p.Gly31Val)

CA396451877

428635 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: d01e4385-09cc-4246-95e1-f8da0cb31e32

HGVS expressions

NM_004360.5:c.92G>T

NM_004360.5(CDH1):c.92G>T (p.Gly31Val)

NC_000016.10:g.68738340G>T

CM000678.2:g.68738340G>T

NC_000016.9:g.68772243G>T

CM000678.1:g.68772243G>T

NC_000016.8:g.67329744G>T

NG_008021.1:g.6049G>T

ENST00000261769.10:c.92G>T

ENST00000261769.9:c.92G>T

ENST00000422392.6:c.92G>T

ENST00000566510.5:c.92G>T

ENST00000566612.5:c.92G>T

ENST00000611625.4:c.92G>T

ENST00000612417.4:c.92G>T

ENST00000621016.4:c.92G>T

NM_004360.3:c.92G>T

NM_001317184.1:c.92G>T

NM_001317185.1:c.-1524G>T

NM_001317186.1:c.-1728G>T

NM_004360.4:c.92G>T

NM_001317184.2:c.92G>T

NM_001317185.2:c.-1524G>T

NM_001317186.2:c.-1728G>T

Likely Benign

PM2_Supporting BS2

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

Evidence Links 0

Expert Panel

CDH1 VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

CDH1 VCEP

The c.92G>T (NM_004360.5) variant in CDH1 is a missense variant predicted to predicted to cause substitution of Gly by Val at amino acid 31 (p.Gly31Val) in exon 2. This variant was observed in more than ten individuals with no DGC, LBC or SRC tumours and whose families do not suggest HDGC (BS2; Invitae, Ambry). This variant is absent from gnomAD 2.1.1 (PM2_Spporting). In summary, this variant meets the criteria to be classified as likely benign for DGLBCS based on the ACMG/AMP criteria applied, as specified by the ClinGen CDH1 VCEP: PM2_Supporting, BS2. (CDH1 VCEP specifications version 3.1; 05/06/2022)

PM2_Supporting

This variant is absent from gnomAD 2.1.1 (PM2_Supporting).

BS2

This variant has been observed in 12 individuals with no DGC, LBC or SRC tumours and whose families do not suggest HDGC (BS2_Supporting; Ambry, Invitae). Note that this includes one individual with LCIS and IDC and one individual with a personal history of breast cancer and family history of gastric cancer.

PS2

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

PS4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PS3

Functional studies not reported.

PS1

No pathogenic missense variants have been reported at this position.

PP4

PP4 is not applicable to CDH1.

PP1

Segregation unknown.

PP3

This variant is not predicted to alter splicing.

PP2

PP2 does not apply to CDH1.

PM3

PM3 is not applicable to CDH1.

PM1

PM1 does not apply to CDH1.

PM4

PM4 does not apply to this variant.

PM5

PM5 does not apply to CDH1.

PM6

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

PVS1

PVS1 does not apply to this variant.

BA1

This variant is absent from gnomAD.

BS4

Segregation unknown.

BS3

Functional studies not reported.

BS1

This variant is absent from gnomAD.

BP5

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

BP7

BP7 does not apply to this variant.

BP2

This variant has not been reported in cis or trans with a pathogenic variant.

BP3

BP3 does not apply to CDH1.

BP4

This variant is not predicted to alter splicing (not applied).

BP1

BP1 does not apply to CDH1.

Approved on: 2023-08-02

Published on: 2023-08-02

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