ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000021.8) (NC_000021.9)
  • Haploinsufficiency score: 3
  • Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
  • Haploinsufficiency Phenotype: AUTISM
Evidence for haploinsufficiency phenotype
PubMed ID Description
27824329 Study sequences 189 autism risk genes in a 1,543 Chinese ASD probands (1,045 from trios). Two de novo DSCAM disrupting variants (defined as nonsense, frameshift or splice site) in 1,086 Chinese ASD trios. Also one maternally inherited DSCAM disrupting variant (maternal phenotype unclear). Also, 20 missense variants, mostly inherited.
25363768 Simons Simplex Collection exome paper, >2500 autism simplex families. Exomes for 2,508 affected children (& parents) and 1,911 unaffected siblings. Three de novo DSCAM disrupting variants in probands (and one de novo missense in an unaffected sibs).
25363760 Autism Sequencing Consortium 2014 paper. Exomes of 3,871 autism cases and 9,937 ancestry-matched or parental controls. One case de novo loss of function, one control loss of function. Controls: 2672 UK 10K case-control - healthy individuals from two intensively studied British cohorts of European ancestry, namely the Avon Longitudinal Study of Parents and Children (ALSPAC)13 and TwinsUK14 2526 Swedish controls - controls were randomly selected from Swedish population registers. Control inclusion criteria: never hospitalized for schizophrenia or bipolar disorder, both parents born in Scandinavia, age?18 years. 861 ARRA Autism Sequencing Consortium case-control - unrelated cases and controls. In total 6059 unrelated controls.

Haploinsufficiency phenotype comments:

DSCAM haploinsufficiency appears fairly well established as a risk factor for autism. However controls with loss of function variants have been reported.

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

Triplosensitivity phenotype comment:

DSCAM is thought to be in the Down Syndrome critical region. There is evidence from animal models that show affects on neurons when present in three copies. No literature for duplication of DSCAM alone in humans.