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.832+1G>A

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA396459027

463795 (ClinVar)

Gene: CDH1

Condition: hereditary diffuse gastric cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: cc34c30c-3789-40a7-9f1b-131a3a3bfb85

Approved on: 2019-11-19

Published on: 2020-01-14

HGVS expressions

NM_004360.5:c.832+1G>A

NM_004360.5(CDH1):c.832+1G>A

NC_000016.10:g.68810342G>A

CM000678.2:g.68810342G>A

NC_000016.9:g.68844245G>A

CM000678.1:g.68844245G>A

NC_000016.8:g.67401746G>A

NG_008021.1:g.78051G>A

ENST00000261769.10:c.832+1G>A

ENST00000261769.9:c.832+1G>A

ENST00000422392.6:c.832+1G>A

ENST00000561751.1:c.455-1342G>A

ENST00000562836.5:n.903+1G>A

ENST00000566510.5:c.676+1G>A

ENST00000566612.5:c.832+1G>A

ENST00000611625.4:c.832+1G>A

ENST00000612417.4:c.832+1G>A

ENST00000621016.4:c.832+1G>A

NM_004360.3:c.832+1G>A

NM_001317184.1:c.832+1G>A

NM_001317185.1:c.-784+1G>A

NM_001317186.1:c.-988+1G>A

NM_004360.4:c.832+1G>A

NM_001317184.2:c.832+1G>A

NM_001317185.2:c.-784+1G>A

NM_001317186.2:c.-988+1G>A

Likely Pathogenic

PVS1_Strong PM2 PS4_Supporting

BP5 BP7 BP4 BP3 BP1 BP2 PS1 PS2 PS3 PP1 PP2 PP3 PP4 BA1 PM6 PM1 PM3 PM5 PM4 BS2 BS1 BS4 BS3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

CDH1 VCEP

The CDH1 c.832+1G>A variant is a canonical splice variant predicted to result in a truncated or absent protein (PVS1_Strong). The variant is absent from the gnomAD cohort (PM2; http://gnomad.broadinstitute.org). This variant was observed in one family meeting IGCLC criteria for HDGC (PS4_Supporting, SCV000637855.2). In summary, this variant meets criteria to be classified as likely pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: PVS1_Strong, PM2, PS4_Supporting.

PVS1_Strong

This variant is at a canonical splice site, and therefore PVS1_Strong is applied.

PM2

This variant is absent from populations in gnomAD, ExAC, 1000 Genomes and ESP.

PS4_Supporting

One family meets IGCLC criteria for HDGC and supports the use of PS4_Supporting (SCV000637855.2).

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 canonical splice site variants.

BP4

BP4 does not apply to canonical splice site variants.

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.

PS1

PS1 does not apply to splicing variants.

PS2

This information is not available.

PS3

To our knowledge, no functional studies for this variant have been reported.

PP1

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

PP2

PP2 does not apply to CDH1.

PP3

PP3 does not apply to canonical splice site variants.

PP4

PP4 does not apply to CDH1.

BA1

This variant is absent from populations in gnomAD, ExAC, 1000 Genomes and ESP.

PM6

This information is not available.

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 canonical splice site variants.

BS2

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

BS1

This variant is absent from populations in gnomAD, ExAC, 1000 Genomes and ESP.

BS4

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

BS3

To our knowledge, no functional studies for this variant have been reported.

Curation History

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