ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000003.11) (NC_000003.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
25138099 Kuechler et al. (2014) performed whole exome sequencing (trio analysis) on a cohort of 301 patients with intellectual disability and identified de novo intragenic variants in SET domain-containing 5 (SETD5) in two unrelated female patients. One patient carried a nonsense variant, and the other an 81 bp deletion located across a splite-donor site. Both intragenic variants were shown to undergo nonsense mediated decay, consistent with a loss-of-function and haploinsufficiency. Genomic microarray analysis of the same cohort identified additional de novo nonfocal microdeletions encompassing the SETD5 gene in 4 unrelated patients (6 total). In addition to ID, all patients with SETD5 alterations in this study were reported to have similar facial dysmorphisms.
24680889 Grozeva et al. (2014) sequenced a cohort of 996 patients with moderate to severe ID by a targeted NGS approach and identified 7 unrelated male patients with de novo heterozygous frameshift or truncating mutations in SETD5. This reference was also reviewed in OMIM (see

Haploinsufficiency phenotype comments:

Heterozygous loss-of-function mutations and deletions affecting SETD5 have been identified in multiple unrelated patients with ID and similar facial features. Additional reports of deletions encompassing SETD5 include Pinto et al., 2014 (PMID 24768552), Peltekova et al., 2012 (PMID 22903836) and Kellogg et al., 2013 (PMID 23613140).

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