ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function 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.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.