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]

Variant: NM_004360.5(CDH1):c.69G>A (p.Gln23=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA193735

186050 (ClinVar)

Gene: CDH1

Condition: hereditary diffuse gastric cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 2823e92b-717a-4984-8f92-73b8b7effb19

Approved on: 2019-11-19

Published on: 2020-01-14

HGVS expressions

NM_004360.5:c.69G>A

NM_004360.5(CDH1):c.69G>A (p.Gln23=)

NC_000016.10:g.68738317G>A

CM000678.2:g.68738317G>A

NC_000016.9:g.68772220G>A

CM000678.1:g.68772220G>A

NC_000016.8:g.67329721G>A

NG_008021.1:g.6026G>A

ENST00000261769.10:c.69G>A

ENST00000261769.9:c.69G>A

ENST00000422392.6:c.69G>A

ENST00000566510.5:c.69G>A

ENST00000566612.5:c.69G>A

ENST00000611625.4:c.69G>A

ENST00000612417.4:c.69G>A

ENST00000621016.4:c.69G>A

NM_004360.3:c.69G>A

NM_001317184.1:c.69G>A

NM_001317185.1:c.-1547G>A

NM_001317186.1:c.-1751G>A

NM_004360.4:c.69G>A

NM_001317184.2:c.69G>A

NM_001317185.2:c.-1547G>A

NM_001317186.2:c.-1751G>A

Likely Benign

BP7 PM2 BS2_Supporting

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

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

CDH1 VCEP

The c.69G>A (p.Glu23=) variant is absent from the gnomAD cohort (PM2; https://gnomad.broadinstitute.org). In silico splice site predictors do not suggest that this variant impacts splicing, and the G allele is not highly conserved across species (BP7).The variant has also been observed in >3 individuals without a diagnosis of diffuse gastric cancer, signet ring tumor or lobular breast cancer and whose family histories do not suggest HDGC (BS2_Supporting; SCV000216307.4, SCV000545385.4, internal laboratory). Experts decide to ignore the conflicting code PM2 in this curation and classify this variant as likely benign. In summary, this variant meets criteria to be classified as likely benign based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: PM2, BP7, BS2_Supporting.

BP7

In silico splice site predictors do not suggest that this variant impacts splicing, and the G allele is not highly conserved across species.

PM2

This variant is absent from gnomAD.

BS2_Supporting

This variant has been observed in nine families not meeting IGCLC criteria for HDGC (SCV000216307.4, SCV000545385.4, internal laboratory).

BP4

BP4 does not apply to this variant.

BP3

BP3 does not apply to CDH1.

BP1

BP1 does not apply to CDH1.

BP2

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

BP5

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

PS1

PS1 does not apply to this variant.

PS2

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

PS3

To our knowledge, this variant has not been evaluated for impact on splicing.

PS4

To our knowledge, this variant has not been reported in individuals meeting IGCLC criteria for HDGC.

PP1

To our knowledge, this variant has not been reported in individuals meeting IGCLC criteria for HDGC.

PP2

PP2 does not apply to CDH1.

PP3

PP3 does not apply to this variant.

PP4

PP4 does not apply to CDH1.

PM6

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

PVS1

PVS1 does not apply to this variant.

PM1

PM1 does not apply to CDH1.

PM3

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

PM5

PM5 does not apply to CDH1.

PM4

PM4 does not apply to this variant.

BA1

This variant is absent from gnomAD.

BS1

This variant is absent from gnomAD.

BS4

To our knowledge, this variant has not been reported in individuals meeting IGCLC criteria for HDGC.

BS3

To our knowledge, this variant has not been evaluated for impact on splicing.

Curation History

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