ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000007.13) (NC_000007.14)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

While haploinsufficiency for GTF2IRD2 alone has not been demonstrated. Deletions involving the 7q11.23 region cause the contiguous gene deletion disorder, Williams-Beuren syndrome (WBS) (MIM #194050). One study (Porter et al. 2012) reported that deletions of this region in WBS patients variably include the GTF2IRD2 gene. Porter MA et al. (2012) (PMID:23118870), performed detailed, neuropsychological profiling in a cohort of patients with typical WBS (1.6 Mb) deletions within 7q11.23 (n=43) and what the authors described as larger, atypical deletions (1.8Mb) including GTF2IRD2 (n=10). The patients with the larger deletions showed "significantly more [cognitive impairment] in the areas of spatial functioning, social reasoning, and cognitive flexibility (a form of executive functioning). They also displayed significantly more obsessions and externalizing behaviours, a likely manifestation of poor cognitive flexibility and executive dysfunction." The authors report that NCF1 and GTF2IRD2 are the only two additional genes deleted in the 1.8Mb deletion, and note that NCF1 "encodes a component of neutrophil NADPH oxidase, which when mutated causes an immunodeficiency condition with no overt neurological phenotype;" they go on to infer that haploinsufficiency of GTF2IRD2 is the more likely explanation of the neuropsychological differences noted in the individuals with larger deletions. At this time, focal deletions of this gene have not been associated with any recognizable clinical phenotype.

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