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>A (p.Leu21Ile)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA10577531

234812 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e3728258-c1cd-4604-a579-317d7dfcaf51

Approved on: 2023-08-21

Published on: 2023-08-21

HGVS expressions

NM_004360.5:c.61C>A

NM_004360.5(CDH1):c.61C>A (p.Leu21Ile)

NC_000016.10:g.68738309C>A

CM000678.2:g.68738309C>A

NC_000016.9:g.68772212C>A

CM000678.1:g.68772212C>A

NC_000016.8:g.67329713C>A

NG_008021.1:g.6018C>A

ENST00000261769.10:c.61C>A

ENST00000261769.9:c.61C>A

ENST00000422392.6:c.61C>A

ENST00000566510.5:c.61C>A

ENST00000566612.5:c.61C>A

ENST00000611625.4:c.61C>A

ENST00000612417.4:c.61C>A

ENST00000621016.4:c.61C>A

NM_004360.3:c.61C>A

NM_001317184.1:c.61C>A

NM_001317185.1:c.-1555C>A

NM_001317186.1:c.-1759C>A

NM_004360.4:c.61C>A

NM_001317184.2:c.61C>A

NM_001317185.2:c.-1555C>A

NM_001317186.2:c.-1759C>A

Uncertain Significance

BS2_Supporting PM2_Supporting

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

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>A (p.Leu21Ile) variant results in a non-synonymous amino acid change in exon 2. The A allele has not been observed in the gnomAD population database (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been observed in at least three individuals without DGC, SRC tumours and whose families do not suggest HDGC (BS2_supporting; SCV000760847.1, SCV000279855.9) 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): PM2_Supporting, BS2_supporting.

BS2_Supporting

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

PM2_Supporting

This variant is absent from gnomAD.

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

PM3

PM3 does not apply to CDH1.

PM1

PM1 does not apply to this variant.

PM4

PM4 does not apply to this variant.

PM5

PM5 does not apply to CDH1.

PVS1

PVS1 does not apply to this variant.

BA1

This variant is absent from gnomAD.

BS4

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

BS3

BS3 does not apply to this variant.

BS1

This variant is absent from gnomAD.

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.

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.

PS2

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

PS4

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

PS3

PS3 does not apply to this variant.

PS1

PS1 does not apply to this variant.

Curation History

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