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_001317186.2:c.-403G>A

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA288037

127914 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 83921f5d-95da-4bbf-9dbe-4afe1c1ec6e6

Approved on: 2023-08-03

Published on: 2023-08-03

HGVS expressions

NM_001317186.2:c.-403G>A

NC_000016.10:g.68815611G>A

CM000678.2:g.68815611G>A

NC_000016.9:g.68849514G>A

CM000678.1:g.68849514G>A

NC_000016.8:g.67407015G>A

NG_008021.1:g.83320G>A

ENST00000261769.10:c.1417G>A

ENST00000261769.9:c.1417G>A

ENST00000422392.6:c.1234G>A

ENST00000562836.5:n.1488G>A

ENST00000566510.5:c.*83G>A

ENST00000566612.5:c.1417G>A

ENST00000611625.4:c.1480G>A

ENST00000612417.4:c.1417G>A

ENST00000621016.4:c.1417G>A

NM_004360.3:c.1417G>A

NM_001317184.1:c.1234G>A

NM_001317185.1:c.-132G>A

NM_001317186.1:c.-403G>A

NM_004360.4:c.1417G>A

NM_004360.5:c.1417G>A

NM_001317184.2:c.1234G>A

NM_001317185.2:c.-132G>A

NM_004360.5(CDH1):c.1417G>A (p.Val473Ile)

Likely Benign

BS2

PS2 PS3 PS4 PP1 PP3 PM6 PM2 BA1 BS4 BS3 BS1 BP5 BP2

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.1417G>A (p.Val473Ile) variant results in a conservative missense change in the Cadherin 3 domain of CDH1. This variant was observed in 5 of 152,172 alleles in the gnomAD v3.1.2 population database. However, this variants has also been observed in more than 10 individuals without GC, DGC, gastric SRC tumours or LBC and whose families do not suggest HDGC (BS2). In summary, this variant meets criteria to be classified as Likely Benign based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: BS2. (CDH1 VCEP specifications version 3.1; 05/22/2023)

BS2

This variant has been observed in ~383 families without HDGC. This variant was also identified in two families with a history of unspecified gastric and gastrointestinal cancer and two probands with ILC in 60s.

PS2

To our knowledge, this variant has not been reported in a proband with HDGC.

PS3

To our knowledge, splicing studies have not been reported for this variant.

PS4

PP1

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

PP3

This variant is not predicted to result in abnormal splicing.

PM6

To our knowledge, this variant has not been reported in a proband with HDGC.

PM2

This variant occurs at a frequency of 3.3x10-5 (5 in 152,172 alleles) in gnomAD.

BA1

This variant occurs at a frequency of 3.3x10-5 (5 in 152,172 alleles) in gnomAD.

BS4

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

BS3

To our knowledge, splicing studies have not been reported for this variant.

BS1

This variant occurs at a frequency of 3.3x10-5 (5 in 152,172 alleles) in gnomAD.

BP5

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

BP2

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

Curation History

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