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.61C>G (p.Leu21Val)

CA10580066

230175 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 8d14ba7e-4b70-4457-a487-62b5bad7739f

HGVS expressions

NM_004360.5:c.61C>G

NM_004360.5(CDH1):c.61C>G (p.Leu21Val)

NC_000016.10:g.68738309C>G

CM000678.2:g.68738309C>G

NC_000016.9:g.68772212C>G

CM000678.1:g.68772212C>G

NC_000016.8:g.67329713C>G

NG_008021.1:g.6018C>G

ENST00000261769.10:c.61C>G

ENST00000261769.9:c.61C>G

ENST00000422392.6:c.61C>G

ENST00000566510.5:c.61C>G

ENST00000566612.5:c.61C>G

ENST00000611625.4:c.61C>G

ENST00000612417.4:c.61C>G

ENST00000621016.4:c.61C>G

NM_004360.3:c.61C>G

NM_001317184.1:c.61C>G

NM_001317185.1:c.-1555C>G

NM_001317186.1:c.-1759C>G

NM_004360.4:c.61C>G

NM_001317184.2:c.61C>G

NM_001317185.2:c.-1555C>G

NM_001317186.2:c.-1759C>G

Uncertain Significance

BS2_Supporting

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

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.61C>G (p.Leu21Val) variant results in a non-synonymous amino acid change in exon 2. This variant is present in 5 of 188,446 alleles (0.00003) in gnomAD, present exclusively in the East Asian subpopulation with 5 of 12,882 alleles (0.00039). This variant has been observed in at least three individuals without DGC, SRC tumour or LBC and whose families do not suggest HDGC (BS2_supporting). In summary, the clinical significance of this variant is uncertain based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2_supporting.

BS2_Supporting

This variant was observed in nine individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (Ambry, GeneDx, Invitae).

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

This variant is present in 5 of 188,446 alleles in gnomAD (0.00003), found exclusively in the East Asian subpopulation with 5 in 12,882 alleles (0.00039).

BP5

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

BP7

BP7 does not apply to this variant.

BP2

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

BP3

BP3 does not apply to CDH1.

BP4

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

BP1

BP1 does not apply to CDH1.

PVS1

PVS1 does not apply to this variant.

PS4

This variant was found in one individual with gastric cancer with diffuse features and a first-degree relative with gastric cancer (GeneDx). However, PS4 not meet since less than 30% reported individuals meet HDGC criteria.

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

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

PP1

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

PP4

PP4 does not apply to CDH1.

PP3

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.

PM6

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

PM2

This variant is present in 5 of 188,446 alleles in gnomAD (0.00003), found exclusively in the East Asian subpopulation with 5 in 12,882 alleles (0.00039).

BA1

This variant is present in 5 of 188,446 alleles in gnomAD (0.00003), found exclusively in the East Asian subpopulation with 5 in 12,882 alleles (0.00039).

PM3

PM3 does not apply to CDH1.

PM1

PM1 does not apply to CDH1.

PM4

PM4 does not apply to this variant.

PM5

PM5 does not apply to CDH1.

Approved on: 2023-08-21

Published on: 2023-08-21

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