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_001195573.1(DICER1):c.5365-142del

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA658656432

477261 (ClinVar)

Gene: DICER1

Condition: dicer1 syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 05c5ac39-e35e-45af-a648-c8e3125e0abb

Approved on: 2022-05-18

Published on: 2022-07-08

HGVS expressions

NM_001195573.1:c.5365-142del

NM_001195573.1(DICER1):c.5365-142del

NC_000014.9:g.95091251del

CM000676.2:g.95091251del

NC_000014.8:g.95557588del

CM000676.1:g.95557588del

NC_000014.7:g.94627341del

NG_016311.1:g.71172del

ENST00000343455.8:c.5479del

ENST00000393063.6:c.5479del

ENST00000526495.6:c.5479del

ENST00000556045.6:c.*196del

ENST00000675540.1:n.3224del

ENST00000675995.1:c.*3795del

ENST00000343455.7:c.5479del

ENST00000393063.5:c.5479del

ENST00000526495.5:c.5479del

ENST00000527414.5:c.5479del

ENST00000527416.2:n.72del

ENST00000527554.2:n.172del

ENST00000541352.5:c.5365-142del

ENST00000556045.5:c.2173del

NM_001271282.2:c.5479del

NM_001291628.1:c.5479del

NM_030621.4:c.5479del

NM_177438.2:c.5479del

NM_001271282.3:c.5479del

NM_001291628.2:c.5479del

NM_177438.3:c.5479del

NM_001395677.1:c.5479del

NM_001395678.1:c.5479del

NM_001395679.1:c.5479del

NM_001395680.1:c.5479del

NM_001395682.1:c.5479del

NM_001395683.1:c.5479del

NM_001395684.1:c.5479del

NM_001395685.1:c.5479del

NM_001395686.1:c.5197del

NM_001395687.1:c.5074del

NM_001395688.1:c.5074del

NM_001395689.1:c.5074del

NM_001395690.1:c.5074del

NM_001395691.1:c.4912del

NM_001395697.1:c.3796del

NR_172715.1:n.5897del

NR_172716.1:n.6081del

NR_172717.1:n.5991del

NR_172718.1:n.5914del

NR_172719.1:n.5747del

NR_172720.1:n.5950del

NM_177438.3(DICER1):c.5479del (p.Leu1827fs)

Pathogenic

PM2_Supporting PS4_Supporting PVS1

BS4 BS3 BS1 BP2 BA1 PM1 PM6 PS2 PS3 PP4 PP1

Evidence Links 0

Expert Panel

DICER1 and miRNA-Processing Gene VCEP

Criteria Specification Information

Criteria Specification: ClinGen DICER1 and miRNA-Processing Gene Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for DICER1 Version 1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

DICER1 and miRNA-Processing Gene VCEP

The NM_177438.2:c.5479del(p.Leu1827fs) variant in DICER1 is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 25/27 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant received a total of 1 phenotype points across 1 proband with PPB, meeting DICER1 VCEP phenotype specificity scoring criteria of 1-1.5 points (PS4_Supporting, SCV000658348.1). This variant is absent from gnomAD v2.1.1 and v3.1.1 (non-cancer) (PM2_Supporting). In summary, this variant meets the criteria to be classified as PATHOGENIC for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: PVS1, PS4_Supporting, PM2_Supporting. (Bayesian Points: 10; VCEP specifications version 1; 02/11/2022)

PM2_Supporting

Absent from gnomAD with >20x coverage in the region.

PS4_Supporting

1 pt. for Invitae case w/ PPB (Same case as International PPB Registry)

PVS1

This variant is predicted to result in NMD due to termination codon upstream of p.Pro1850 (p.Leu1827TrpfsTer11)

BS4

Insufficient data

BS3

None found

BS1

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

BP2

Co-inherited c.*5G>A and c.1168T>C (p.Tyr390His), phases unknown in case from Prevention with suspected CCAM. Variants are conflicting (LB/VUS) in ClinVar and not VCEP-curated.

BA1

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

PM1

Not a missense variant

PM6

Not observed

PS2

Not observed

PS3

None found

PP4

No tumor data

PP1

Insufficient data

Curation History

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