DICER1 p.Arg293fs
c.878_881del · rs886037733 · VCV254355
ClinGen expert panel — DICER1 and miRNA-Processing Gene VCEP
Pathogenic for dicer1 syndrome. Applied ACMG criteria (verbatim):
PVS1 PM2_Supporting PS4_Supporting PP4
Curation rationale (ClinGen, verbatim)
The NM_177438.2:c.878_881del (p.Arg293fs) variant in DICER1 is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 7/27 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 point across 1 proband meeting DICER1 VCEP phenotype specificity scoring criteria of 1-1.5 points (PS4_Supporting, PMID: 26925222). This individual was found to have a somatic second hit in a recognized DICER1 hotspot codon on tumor sequencing, which is highly specific for DICER1 syndrome (PP4, PMID: 26925222). 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, PP4, PM2_Supporting. (Bayesian Points: 11; VCEP specifications version 1; 02/11/2022)
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 7 of 27 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP -1.1, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- DICER1
- Protein
- p.Arg293fs
- Coding
- c.878_881del
- MANE Select
- NM_177438
- dbSNP
- rs886037733
- Type
- Deletion
- Location
- chr14:95126602 (GRCh38)
- Gene constraint
- LOEUF 0.275 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.89 · 21 PDB
- Residue 293
- the 'required for interaction with prkra and tarbp2' region
Disease context
DICER1-related tumor predisposition — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: hereditary neoplastic syndrome
For DICER1 tumor-predisposition syndrome (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Adolescent, Adult, Childhood
- Prevalence
- <1 / 1 000 000 (Worldwide)
Similar variants
- DICER1 p.Arg293Gly Uncertain significance ★★ ⚠ same residue
- DICER1 p.Arg293= Likely benign ★ same residue
- DICER1 p.Glu292fs Likely pathogenic ★★★ same condition
- DICER1 p.Ile627fs Pathogenic ★★★ same condition
- DICER1 p.Leu1827fs Pathogenic ★★★ same condition
- DICER1 p.Met842fs Pathogenic ★★★ same condition
- DICER1 c.2650+5_2650+7del Uncertain significance ★★★ same condition
- DICER1 c.1752+1del Pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dicer1-p-arg293fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown