ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

  • 2p23.2-p23.1
  • GRCh37/hg19 chr2: 29,415,640-30,144,477
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr2: 29,190,992-29,921,589
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000002.11) (NC_000002.12)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Germline, gain of function mutations in ALK result in neuroblastic tumor susceptibility (Mosse et al. 2018, 18724359), via constitutive phosphorylation, consistent with activation and resulting in profound growth inhibition. Mutations are mainly located in the tyrosine kinase domain and explain the majority of hereditary neuroblastomas. A germline intragenic deletion in ALK was found in a patient with meduloblastoma (Coco et al 2012) but parental studies were not available and expression studies in the tumor showed normal ALK mRNA expression, so its role is currently unclear.

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

Triplosensitivity phenotype comment:

At this time there is no evidence to support the triplosensitivity of this gene. While a constitutional microduplication of 2p involving the ALK and MYCN genes has been described, duplication of MYCN without ALK has been seen with the same phenotype, indicating that duplications of ALK are not causing the phenotype (Van Mater et al. 2013, PMID 23401364)