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
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.

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.