ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000002.11) (NC_000002.12)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
25363760 De Rubeis S et. al., 2014 . This group conducted autism spectrum disorder (ASD) WES study, analyzing 3,871 ASD cases. In child ID 10C110254, one de novo nonsense mutation (g.39053113G>A) was found in DHX57 gene (supplemental table 2). In this specimen, there is another de novo mutation identified, but it is a synonymous variant in BAIAP2 gene.
28263302 C Yuen RK et. al., 2017. This group performed WGS on 5,205 samples from families with autism spectrum disorder (ASD). Both complete genomics WGS and CMA were performed on the sample 1-0826-004, and 83 de novo SNV and indels were found (supplemental table 2), including a de novo nonsense mutation (g.39090540G>A) (supplemental table 4). This variant is the only LOF variant seen in this specimen. DHX57 is not listed as one of the 18 new candidate ASD risk genes in this study.

Haploinsufficiency phenotype comments:

So far, there are only two independent de novo LOF mutations (both are nonsense mutations) in unrelated individuals with ASD reported in two publications. However, ExAC PLI score is 0 and both of these two variants have been seen in ExAC database. g.39053113G>A has been seen 2/121358, allele freq=0.00001648; g.39090540G>A has been seen 27/121252, allele freq=0.0002227. After group discussion, hap score is 0 based on population freq data.

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