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]

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Variant: NM_004360.5(CDH1):c.394G>A (p.Val132Ile)

CA168677

142546 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: d1ca0483-4cad-4216-96ee-2346b5002470

Approved on: 2023-08-03

Published on: 2023-08-03

HGVS expressions

NM_004360.5:c.394G>A

NM_004360.5(CDH1):c.394G>A (p.Val132Ile)

NC_000016.10:g.68808430G>A

CM000678.2:g.68808430G>A

NC_000016.9:g.68842333G>A

CM000678.1:g.68842333G>A

NC_000016.8:g.67399834G>A

NG_008021.1:g.76139G>A

ENST00000261769.10:c.394G>A

ENST00000261769.9:c.394G>A

ENST00000422392.6:c.394G>A

ENST00000561751.1:n.161G>A

ENST00000562836.5:n.465G>A

ENST00000564676.5:n.676G>A

ENST00000564745.1:n.389G>A

ENST00000566510.5:c.394G>A

ENST00000566612.5:c.394G>A

ENST00000611625.4:c.394G>A

ENST00000612417.4:c.394G>A

ENST00000621016.4:c.394G>A

NM_004360.3:c.394G>A

NM_001317184.1:c.394G>A

NM_001317185.1:c.-1222G>A

NM_001317186.1:c.-1426G>A

NM_004360.4:c.394G>A

NM_001317184.2:c.394G>A

NM_001317185.2:c.-1222G>A

NM_001317186.2:c.-1426G>A

Likely Benign

BS2

PM6 PM2 PM4 PM3 PM1 PM5 BS4 BS3 BS1 BP3 BP4 BP1 BP2 BP5 BP7 PS4 PS2 PS3 PS1 PVS1 BA1 PP1 PP4 PP3 PP2

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 NM_004360.5(CDH1):c.394G>A (p.Val132Ile) variant has been observed in >10 individuals without a diagnosis of diffuse gastric cancer, signet ring tumor or lobular breast cancer and whose family histories do not suggest HDGC (BS2; internal laboratory contributors). In summary, the clinical significance of this variant is classified as likely benign based on BS2 alone. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel: BS2. (CDH1 VCEP specifications version 3.1; 04/24/2023)

BS2

This variant has been observed in 213 heterozygous individuals with no diffuse gastric cancer, signet ring cell carcinoma or lobular breast cancer and/or whose family histories do not suggest HDGC (BS2; GeneDX, Ambry, Invitae). Note that this includes one individual with family history of unspecified gastric cancer.

PM6

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

PM2

Allele frequency is not at extremely low frequency or absent from controls

PM4

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

PM3

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

PM1

Not applicable

PM5

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

BS4

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

BS3

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

BS1

Allele frequency is not greater than expected due to disorder

BP3

Not applicable

BP4

Not applicable

BP1

Not applicable

BP2

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

BP5

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

BP7

Not applicable

PS4

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

PS2

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

PS3

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

PS1

Not applicable

PVS1

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

BA1

Allele frequency is less than 5% in ExAC, 1000 Genomes, or ESP

PP1

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

PP4

Not applicable

PP3

Not applicable

PP2

Not applicable

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