ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
29302074 Hu et al. (2018) - Report on whole exome and whole genomes sequencing in 404 consanguineous Iranian families with two or more affected individuals. A single homozygous frameshift variant (p.Ser735Valfs*125) identified in a region of homozygosity reported. This family (#M8700057) had 3 affected individuals with moderate ID however unclear if they are stating that this variant segregates with phenotype. Parents are reported as first cousins. Per pedigree (pg64 of supplemental info), parents are denoted as unaffected however not clearly stated. HIVEP3 suggested as a novel autosomal recessive ID candidate gene.
27824329 Wang et al. (2016) - De novo single likely gene disrupting (sLGD) variant (c.1753dupC) reported (in supplemental data) in a cohort study of de novo genic mutations among a Chinese autism spectrum disorder cohort. Reported as a candidate gene. **This patient has the same identifier as the Iossifov et al (2014) paper that is listed as an additional report (a few overlapping authors) with the same de novo variant**
25849321 Li et al. (2016) - Study focusing on exonic de novo mutations shared across four neuropsychiatric disorders: autism spectrum disorder, epileptic encephalopathy, intellectual disability and schizophrenia, in addition to unaffected siblings (control), from 36 studies by WES/WGS [17,104 de novo mutations from 3,555 trios]. Two de novo nonsense variants reported: Q934X identified from a schizophrenia cohort (from Fromer et al, 2014) and Q2200X identified from an ASD cohort.

Haploinsufficiency phenotype comments:

Various disease associations - schizophrenia, autism, ID for LOF variants. Missense variants a/w very early onset inflammatory bowel disease. Not sure how to count the Hu et al paper suggesting this as an ARID candidate gene with parents being carriers and not documented as affected. gnomad pLI = 0.88/ExAC pLi = 0.03. LOF variants smattered along protein (no-hot spots)

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