ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000002.11) (NC_000002.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
25170348 Gazzellone et. al. 2014. This group tested 104 ASD probands and their parents who were recruited from Harbin, China. Samples were genotyped on the Affymetrix CytoScan HD platform. Rare CNVs were identified by comparing data with 873 technology-matched controls from Ontario and 1,235 additional population controls of Han Chinese ethnicity. Sample ID 683-3 carried a de novo 22kb deletion contains 7 exons ( exons 11-17 of the longest transcript) of GIGYF2 gene (chr2(GRCh37): 233,651,280-233,673,273).
25363768 Iossifov et al. 2014. This group sequenced exomes from more than 2,500 simplex families (Simons Simplex Collection: probands in the current sample exhibit moderate to severe autistic symptoms with relatively little intellectual disability). In family 14533, a de novo variant chr2(GRCh37):g.233675982:C>T nonsense mutation was identified (not seen in gnomad).
27824329 Wang et al. 2016.They sequence 189 risk genes in 1,543 Chinese ASD probands (1,045 from trios). A de novo nonsense mutation (chr2(GRCh37):g.233655745G>T, NM_001103146.1:c.958G>T, p.Glu320*) in GIGYF2 in proband M23762. The patient with a GIGYF2 DN LGD mutation also has mild ID and macrocephaly. A non- maternally inherited frame-shift mutation (Chr2(GRCh37):g.233709081_233709092del, NM_001103146.1:c.3102_3113del, p.Ser1035_His1038del) in GIGYF2 in proband M15067.

Haploinsufficiency phenotype comments:

At least three de novo LOF variants have been reported in patients with ASD in three studies; however, given the non-specific phenotype, and the possible additional assocation with Parkinson's disease (see OMIM for additional information), more evidence is required to determine the role of haploinsufficiency in this gene.

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