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.5G>T (p.Gly2Val)

CA10583400

239909 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: fcab5afd-fdd3-42f2-80d2-b7981264e7a7

HGVS expressions

NM_004360.5:c.5G>T

NM_004360.5(CDH1):c.5G>T (p.Gly2Val)

NC_000016.10:g.68737420G>T

CM000678.2:g.68737420G>T

NC_000016.9:g.68771323G>T

CM000678.1:g.68771323G>T

NC_000016.8:g.67328824G>T

NG_008021.1:g.5129G>T

ENST00000261769.10:c.5G>T

ENST00000261769.9:c.5G>T

ENST00000422392.6:c.5G>T

ENST00000566510.5:c.5G>T

ENST00000566612.5:c.5G>T

ENST00000611625.4:c.5G>T

ENST00000612417.4:c.5G>T

ENST00000621016.4:c.5G>T

NM_004360.3:c.5G>T

NM_001317184.1:c.5G>T

NM_001317185.1:c.-1611G>T

NM_001317186.1:c.-1815G>T

NM_004360.4:c.5G>T

NM_001317184.2:c.5G>T

NM_001317185.2:c.-1611G>T

NM_001317186.2:c.-1815G>T

Uncertain Significance

PM2_Supporting

BA1 PVS1 BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7 PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 PM3 PM1 PM4 PM5 PM6

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 CDH1 c.5G>T (p.Gly2Val) variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). To our knowledge, this variant has not been reported in the literature. In summary, this variant meets criteria to be classified as a variant of uncertain significance based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PM2_Supporting.

PM2_Supporting

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

BA1

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

PVS1

PVS1 does not apply to this variant.

BS2

This variant was observed in one individual without DGC or SGC tumours and whose family does not suggest HDGC (Invitae). However, the proband had a personal history of bilateral breast cancer of unspecified pathology. Therefore, BS2 cannot be applied to this case.

BS4

This information is not available.

BS3

BS3 does not apply to missense variants.

BS1

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

BP2

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

BP3

BP3 does not apply to CDH1.

BP4

BP4 does not apply to missense variants.

BP1

BP1 does not apply to CDH1.

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 missense variants.

PS2

This information is not available.

PS4

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

PS3

PS3 does not apply to missense variants.

PS1

To our knowledge, there are no pathogenic variants in codon 2 of CDH1.

PP4

PP4 does not apply to CDH1.

PP1

This information is not available.

PP3

PP3 does not apply to missense variants.

PP2

PP2 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 missense variants.

PM5

PM5 does not apply to CDH1.

PM6

This information is not available.

Approved on: 2023-08-21

Published on: 2023-08-21

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