ClinGen Dosage Sensitivity Curation Page

KDM6B

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
25363768 Iossifov et al. (2014) identified four unrelated males with autism spectrum disorder (ASD) who harbored de novo sequence variants in KDM6B. Whole exome sequencing identified a splice-site and frame-shift variant in two unrelated males with autism spectrum disorder. Sample ID: 11329 (Supplementary Table 2) harbored a spice-site variant (Chr17:7749188A>G, c.138-2A>G) while sample ID: 12683 (Supplementary Table 2) harbored a frame-shift variant (Chr17:7749921CG>C, c.575del). Neither of these variants were observed in gnomAD as of November 2018. Of note, sample ID: 12683 was reported previously in Iossifov et al. (2012; PMID: 22542183). Two additional de novo variants were observed in an additional two unrelated males with autism spectrum disorder. Sample ID: 13675 (Supplementary Table 2) harbored a 3 base pair synonymous deletion (17:7755287ACTT>A, c.4185_4187del) while sample ID: 13446 (Supplementary Table 2) harbored a single base pair intron substitution (17:7755659G>C, c.4468+5G>C). Neither of these variants were observed in gnomAD as of November 2018.

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.