ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000016.9) (NC_000016.10)
  • Haploinsufficiency score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
28263302 Yuen et al - MSSNG project, WGS, autism study, 2,066 families, one de novo LOF in SRCAP exon 27
25363768 Iossifov et al - Simons Simplex Collection, WES, autism study, 2,517 families, one de novo LOF in SRCAP exon 29

Haploinsufficiency phenotype comments:

SRCAP has a well established association with Floating-Habor syndrome via a dominant negative mechanism: Hood et al (2012, PMID:22265015) reported 5 mutations (nonsense or frameshift) in 13 patients with Floating-Harbor syndrome. Parental specimens were available for testing in 6 cases and all were de novo. However, based on a study done by Monroy et al (2001, PMID:1152279), the non-random clustering of the mutations, and two HapMap control individuals with deletions involving SRCAP, Hood et al. conclude that these mutations likely result in a dominant-negative effect. Additionally, Le Goff et al (2013, PMID:22965468) reported the same mutations in 6 of 9 patients with Floating-Harbor syndrome and Reschen et al (2012, PMID:23165645) reported one patient with a recurrent mutation. See also PMID 25326637: Lee et al - WES, clinical service, 814 cases, one de novo LOF in SRCAP (p.Arg2435*) in patient with develomental delay, speech delay, short stature, microcephaly, dysmorphic features, ptosis, brachydactyly, Coffin-Siris syndrome, Kabuki. This patient is consistent with Floating-Habor as well. Following re-review of this gene, there are also 2 de novo LOFs in patients with autism (PMID 28263302 & 25363768). Therefore, an updated haploinsufficiency score of 1 has been assigned.

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