ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

  • 1p36.21-p36.13
  • GRCh37/hg19 chr1: 16,174,359-16,266,950
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr1: 15,847,707-15,940,456
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000001.10) (NC_000001.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
25363768 Iossifov et al. reported a de novo frameshift variant c.3028_3029insA/p.D1011Gfs*11 in an ASD patient
27525107 Yuen et al. reported a de novo nonsense variant c.5392C>T/p.Q1798* in an ASD patient.
28135719 DDD study reported two de novo LOF variants (c.6958_6962del5 /p.K2320Gfs*37 and c.7503G>A/p.W2501*) in patients with developmental disorder.

Haploinsufficiency phenotype comments:

Coe et al. (2018 PMID: 30559488) summarised the de novo variants in SPEN (as one of DD genes) previously reported/detected in three above mentioned papers among patients with developmental disorders by trio exome sequencing. There are a total of four likely gene disruption (LGD) variants and four missense variants so far reported. All de novo variants are listed in Given the high genetic heterogeneity and relatively non-specific nature of this phenotype (ie. ASD/ID/DD), the dosage score for HI is 1. De novo SPEN variants reported in the Krupp 2017 and Stessman 2017 papers are likely from the same individuals due to overlapping cohorts, and are not double counted. Additionally, none of the 4 de novo variants appear in gnomAD.

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

Triplosensitivity phenotype comment:

At this time, no whole-gene duplications of SPEN have been reported.