ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000002.11) (NC_000002.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
25670083 Wegert et al. (2015) analyzed 58 blastemal type Wilms tumors by exome and transcriptome sequencing. Possible germline variants were also checked wherever DNA from blood leukocytes or adjacent normal kidney was available. There were 8 cases with germline variants in genes including DIS3L2 (Y137C, P514X, and Q827X), and some are predicted to be deleterious (Table S4). Only the DIS3L2 P514X mutation became homozygous in the tumor, supportive of functional importance. These constitutional heterozygous mutations appear compatible with normal development, but may still pose an increased tumor risk.
31350202 Ow et al. (2019) utilized next generation sequencing (NGS) to characterize the mutation profile of 174 Asian patients with cancer. 1 patient that meet the Bethesda criteria of Lynch syndrome had a nonsense variant in DIS3L2 gene (p.R724X), which is not in the control database such as ExAC or 1000 Genomes. No further detail provided.
26822237 Parson et al (2016) performed combined tumor and germline WES for 121 children with wide variety of solid tumors. One patient with Wilms tumor had a frame shift variant in DIS3L2 gene (c.2381delG, p.R794fs) and LOH detected in the tumor. However, this variant was inherited from a parent of unknown phenotype (eTable 10).

Haploinsufficiency phenotype comments:

Exon 9 (of 21) and 3? (e15-21) of the gene is highly polymorphic for del CNVs. 3? of the gene also overlaps with SD cluster. Although there are emerging evidence of predicted LOF variants reported as mentioned above, no functional study was performed so far.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

no evidence for triplosensitivity