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.61C>G (p.Leu21Val)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10580066

230175 (ClinVar)

Gene: CDH1

Condition: hereditary diffuse gastric cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

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

Approved on: 2020-07-21

Published on: 2020-09-16

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 PS4_Supporting

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

Evidence Links 0

Expert Panel

Criteria Specification Information

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: 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).

PS4_Supporting

This variant was found in one individual with gastric cancer with diffuse features and a first-degree relative with gastric cancer (GeneDx).

PS1

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

PP1

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.

PP3

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.

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).

PM1

PM1 does not apply to CDH1.

PM3

PM3 does not apply to CDH1.

PM5

PM5 does not apply to CDH1.

PM4

PM4 does not apply to this variant.

PVS1

PVS1 does not apply to this variant.

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).

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

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.

BP4

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.

BP1

BP1 does not apply to CDH1.

BP2

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

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).

Curation History

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