ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

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Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
24307393 Authors did whole genome and targeted sequencing in 9 patients with isolated intellectual disability (ID) of variable degrees without any copy number variations using SNP microarray. The 9 patients were selected from an initial cohort of 236 ID patients which had a medical record review and were determined to have isolated ID based on inclusion criteria set by authors. A de novo splice site mutation in trio 2 was identified suggesting that KDM5B may be a possible ID related candidate gene. No functional studies were performed.
28720891 Authors used whole exome sequencing in an attempt to identify risk genes or rare variants in a cohort of 19 proband-parent trios from singleton families with autism spectrum disorder from Saudi Arabia. Among the 19 probands, one proband (Patient 19) was found to have a de novo nonsense variant p.Y755X in the KDM5B gene. No functional studies were performed.
25363768 Whole exome sequencing of the Simons simplex collection including unaffected sibling and parent in each family was done. Results showed KDM5B as one of the recurrently mutated genes. Figure 2 and supplementary Table 2 showed a total of 4 de novo mutations in KDM5B identified in four ASD probands (2 likely gene disrupting and 2 missense) and 4 occurring in unaffected siblings (2 likely gene disrupting and 2 missense) . None of the 8 individuals appear to be related based on family ID in Table 2. No functional studies or further discussion on KDM5B was done.

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.