ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

  • 10q25.2
  • GRCh37/hg19 chr10: 112,679,128-112,773,425
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr10: 110,919,370-111,013,665
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000010.10) (NC_000010.11)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
24739123 Chen et al. (2014): This paper describes a child with Noonan-like phenotype who has a 183Kb deletion of SHOC2 and another gene, BBIP1. Child was referred for a complex heart defect and clinical evaluation revealed dysmorphic features, microcephaly and normal intelligence with hyperactivity. The authors propose that haploinsufficiency of SHOC2 resulted in the phenotype. The contribution of BBIP1 to the phenotype is uncertain.

Haploinsufficiency phenotype comments:

SHOC2 is a scaffold protein in the ERK1/2 pathway, which tethers RAS, RAF-1 and the catalytic subunit of protein phosphatase 1c (PP1c). Only a few specific missense mutations have been identified in association with a RAS-opathy-like phenotype [PMID:19684605, 25137548]. In these cases, the mutant protein was functional but impaired, leading to abnormal signaling, localization and/or assembly of the SHOC2/RAS/RAF1/PP1c complex. Evidence to support haploinsufficiency of this gene is very limited.

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