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
28139846 In 2017, Zarate et al. used whole exome sequencing (WES) on 11 individuals with SATB2-associated syndrome. The authors identified pathogenic variants in SATB2 in these individuals, all of which were confirmed de novo. Of these variants, 1 was a splice site, 5 were frameshifts, and 3 were nonsense variants.
28151491 In 2017, Bengani et al. described 20 individuals with SATB2 variants identified through whole exome sequencing. Analysis identified 19 different variants in SATB2, with the same variant existing in a pair of siblings. The majority of these individuals were identified from the DDD study. 11 of these variants were de novo loss of function variants, with 4 variants being nonsense variants, 5 being frameshift variants, and 2 being splice site variants. In addition to ID, many of the individuals in this study also had severe speech impairment, drooling, and craniofacial abnormalities including cleft palate and mild dental differences. Per the authors, ?The behavioral phenotype appeared to show the most marked discrepancy within the cohort, with both severe autistic features and friendly/happy personalities being recurrently reported.?

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.