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.49-3C>A

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA16620228

421050 (ClinVar)

Gene: CDH1

Condition: CDH1-related diffuse gastric and lobular breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 1e714af0-0962-48c1-8233-fdf4cbbd84b3

Approved on: 2023-08-21

Published on: 2023-08-21

HGVS expressions

NM_004360.5:c.49-3C>A

NM_004360.5(CDH1):c.49-3C>A

NC_000016.10:g.68738294C>A

CM000678.2:g.68738294C>A

NC_000016.9:g.68772197C>A

CM000678.1:g.68772197C>A

NC_000016.8:g.67329698C>A

NG_008021.1:g.6003C>A

ENST00000261769.10:c.49-3C>A

ENST00000261769.9:c.49-3C>A

ENST00000422392.6:c.49-3C>A

ENST00000566510.5:c.49-3C>A

ENST00000566612.5:c.49-3C>A

ENST00000611625.4:c.49-3C>A

ENST00000612417.4:c.49-3C>A

ENST00000621016.4:c.49-3C>A

NM_004360.3:c.49-3C>A

NM_001317184.1:c.49-3C>A

NM_001317185.1:c.-1567-3C>A

NM_001317186.1:c.-1771-3C>A

NM_004360.4:c.49-3C>A

NM_001317184.2:c.49-3C>A

NM_001317185.2:c.-1567-3C>A

NM_001317186.2:c.-1771-3C>A

Uncertain Significance

BS2_Supporting

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

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.49-3C>A variant has been observed in at least three individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2_supporting; SCV000822625.1, SCV000570129.4, SCV000665064.2). In summary, the clinical significance of this variant is uncertain based on ACMP/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 five individuals without DGC, SRC tumour or LBC and whose families do not suggest HDGC (Ambry, GeneDx, Invitae). However, this variant has also been found in two individuals with notable personal and family history: one individual with breast cancer and a second-degree relative with gastric cancer, both in 70s (Invitae), and one individual with IDC and ILC in 50s and first-degree relative with gastric cancer in 70s (GeneDx).

PS4

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

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

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.

PVS1

PVS1 does not apply to this variant.

BA1

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

PM5

PM5 does not apply to CDH1.

PM3

PM3 does not apply to CDH1.

PM1

PM1 does not apply to CDH1.

PM4

PM4 does not apply to this variant.

PM6

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

PM2

Appear once in gnomAD v3 with 1 out of 42044 alleles in African population.

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

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

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

Some splice site predictors do not suggest that this variant alters splicing. However, HSF predicts that this variant may alter the wild-type acceptor site.

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

The C nucleotide is conserved across multiple mammalian species.

Curation History

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