• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
DICER1 (HGNC:17098) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
dicer 1, ribonuclease III
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
MNG1
Alias symbols
Dicer, KIAA0928, K12H4.8-LIKE, HERNA
%HI
1.99(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.17(Read more about gnomAD LOEUF score)
Cytoband
14q32.13
Genomic Coordinates
GRCh37/hg19: chr14:95552565-95624347 NCBI Ensembl UCSC
GRCh38/hg38: chr14:95086228-95158010 NCBI Ensembl UCSC
MANE Select Transcript
NM_177438.3 ENST00000343455.8 (Read more about MANE Select)
Function
Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing. Cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3' overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs. SiRNAs and miRNAs serve as guide to direct the RNA-induced silencing complex (RISC) to complementary RNAs to degrade them... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-6087
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
02/09/2022

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • DICER1-related tumor predisposition Monarch
HI Evidence:
  • PUBMED: 26925222
    Brenneman, et al. (2015) analyzed 124 pleuropulmonary blastoma (PPB) pediatric cases and their family members. Sequencing of DICER1 revealed 84 heterozygous loss of function variants (including 33 nonsense, 44 frameshift, 6 consensus splice site variants, and deletion of 24th exon) in PPB cases. Out of 75 cases with family data, the variants were inherited in 67 cases, and for 8 cases the data was inconclusive.
  • PUBMED: 19556464
    Hill, et al. (2009) presented 11 pleuropulmonary blastoma families. Direct sequencing of DICER1 revealed heterozygous loss of function variants (including 7 nonsense, and 3 frameshift variants) in 10 families. These variants were absent or sufficiently rare in gnomAD as of February 2022.
  • PUBMED: 21266384
    Slade, et al. (2011) analyzed 823 unrelated cases with different tumors. Sequencing of DICER1 revealed loss of function variants (including 7 frameshift, 2 nonsense, and 1 canonical splice site variant) in 10 pleuropulmonary blastoma cases (age at diagnosis between 1 and 7 years; current age between 1 and 15 years (one patient deceased at age of 5)). In all cases the variant has been inherited. These variants were absent or sufficiently rare in gnomAD as of February 2022.
  • PUBMED: 25118636
    Stewart, et al. (2014) analyzed 12 pleuropulmonary blastoma (PPB) cases (7 females and 5 males). Sequencing of DICER1 revealed 8 loss of function variants (including 3 frameshift, 3 nonsense, and 2 canonical splice site variants) in 8 cases, respectively. These variants were absent in gnomAD as of February 2022.
  • PUBMED: 28624956
    Cai, et al. (2017) analyzed 12 pleuropulmonary blastoma (PPB) pediatric Chinese cases (8 females and 4 males; age at diagnosis between 19 and 77 months (median 36 months)) and their family members. Sequencing of DICER1 revealed 7 heterozygous loss of function variants (including 3 frameshift, 3 nonsense, and 1 canonical splice site variant) in PPB cases. The variants were inherited in 4 families and de novo in 3 families. These variants were absent in gnomAD as of February 2022.
  • PUBMED: 22180160
    Doros, et al. (2012) analyzed 4 pleuropulmonary blastoma (PPB) pediatric cases (age at PPB diagnosis between 5 months and 9 years; 2 males and 2 females). Sequencing of DICER1 revealed 4 loss of function variants (including p.D1437fs, p.Q1726X, p.Y749X, and p.Y637fs) in all 4 cases, respectively. These variants were absent in gnomAD as of February 2022.
HI Evidence Comments:
Heterozygosity for germline loss-of-function-type mutation (nonsense, frameshift, and exonic deletions) of DICER1 is associated with DICER1 syndrome, a familial tumor susceptibility syndrome characterized by increased susceptibility to develop several rare childhood tumors including pleuropulmonary blastoma; ovarian sex cord-stromal tumors (especially Sertoli-Leydig cell tumor); cystic nephroma; and thyroid gland neoplasias. Penetrance for these phenotypes is unknown, but appears to be reduced. As yet, whole gene deletion of DICER1 has not been reported. PMID 24761742 corresponds to the GeneReviews for this condition, which provides a comprehensive overview of the variant spectrum.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000014.8) (NC_000014.9)