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.940A>T (p.Lys314Ter)

CA396459763

428632 (ClinVar)

Gene: CDH1 (HGNC:999)

Condition: CDH1-related diffuse gastric and lobular breast cancer (MONDO:0007648)

Inheritance Mode: Autosomal dominant inheritance

UUID: 8277d227-4d10-4ebb-bc74-fee3cba23a52

Approved on: 2023-08-25

Published on: 2023-08-25

HGVS expressions

NM_004360.5:c.940A>T

NM_004360.5(CDH1):c.940A>T (p.Lys314Ter)

NC_000016.10:g.68811791A>T

CM000678.2:g.68811791A>T

NC_000016.9:g.68845694A>T

CM000678.1:g.68845694A>T

NC_000016.8:g.67403195A>T

NG_008021.1:g.79500A>T

ENST00000261769.10:c.940A>T

ENST00000261769.9:c.940A>T

ENST00000422392.6:c.940A>T

ENST00000561751.1:n.562A>T

ENST00000562836.5:n.1011A>T

ENST00000566510.5:c.784A>T

ENST00000566612.5:c.940A>T

ENST00000611625.4:c.940A>T

ENST00000612417.4:c.940A>T

ENST00000621016.4:c.940A>T

NM_004360.3:c.940A>T

NM_001317184.1:c.940A>T

NM_001317185.1:c.-676A>T

NM_001317186.1:c.-880A>T

NM_004360.4:c.940A>T

NM_001317184.2:c.940A>T

NM_001317185.2:c.-676A>T

NM_001317186.2:c.-880A>T

Pathogenic

PVS1 PM2_Supporting PS4_Supporting PM5_Supporting

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

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 c.940A>T (p.Lys314Ter) variant is predicted to result in a premature termination codon in exon 7 (PVS1, PM5_Supporting). The variant is absent from the gnomAD population database (PM2_Supporting; https://gnomad.broadinstitute.org/). This variant has previously been reported in one individual meeting IGCLC criteria for HDGC (PS4_Supporting; PMID: 26182300). In summary, this variant meets criteria to be classified as pathogenic based on ACMP/AMP criteria as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_Supporting, PS4_Supporting, PM5_Supporting.

PVS1

This variant results in a premature termination codon in exon 7.

PM2_Supporting

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

PS4_Supporting

This variant was reported in one individual meeting IGCLC criteria for HDGC based on a personal and family history of diffuse gastric cancer (PMID: 26182300).

PM5_Supporting

Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.

BS4

To our knowledge, segregation of this variant has not been reported.

BS3

BS3 does not apply to this variant.

BS1

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

BS2

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

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 observed in cis or trans with a known pathogenic variant.

BP3

BP3 does not apply to CDH1.

BP4

BP4 does not apply to this variant.

BP1

BP1 does not apply to CDH1.

BA1

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

PS2

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

PS1

PS1 does not apply to this variant.

PS3

PS3 does not apply to this variant.

PP4

PP4 does not apply to CDH1.

PP1

To our knowledge, segregation of this variant has not been reported.

PP3

PP3 does not apply to this variant.

PP2

PP2 does not apply to CDH1.

PM6

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

PM3

PM3 does not apply to CDH1.

PM1

PM1 does not apply to this variant.

PM4

PM4 does not apply to this variant.

Curation History

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