ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
28191889 Using targeted sequencing of 91 candidate neurodevelopmental disorder genes, Stessman et al., describe 2 patients with de novo frameshift mutations predicted to disrupt the ASH1L gene. In addition, they reference 3 previously described de novo nonsense and frameshift ASH1L mutations. Collectively, the patients had mild to moderate intellectual disability (5/5), autism spectrum disorders (3/5) and seizures (2/5).
25363760 De Rubeis et al., performed whole exome sequencing of of 3871 autism cases and detected two de novo loss-of-function mutations in ASH1L in autism probands. Additional phenotypic information was not available for these two patients.
28263302 Yuen et al., performed whole genome sequencing of 2620 patients with autism spectrum disorders and detected one de novo loss-of-function mutation. Additional phenotypic information was not available for this patient.

Haploinsufficiency phenotype comments:

Additional manuscripts (PMIDs 26350204, 25363768 and others) describe single de novo loss-of-function ASH1L mutations. While most of the mutations described were detected by whole exome or whole genome screening of large patient cohorts and focal deletions of ASH1L have not been published, the supporting statistical analyses and the distribution of de novo loss-of-function mutations in this gene are consistent with a haploinsufficiency mechanism. In addition, many other de novo missense mutations have been described.

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

Triplosensitivity phenotype comment:

No current evidence for triplosensitivity.