See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on variants detected in this gene.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

In families with two or more first-degree relatives with neuroblastoma, the incidence of germline ALK pathogenic variants is 80%. In families in which two second-degree or more distant relatives have neuroblastoma, the incidence of germline ALK pathogenic variants is much lower [Mossé et al 2008].

Somatic ALK activating pathogenic variants, which may be found in 7%-8% of sporadic neuroblastoma tumors, are rarely associated with germline ALK pathogenic variants [Liu & Thiele 2012]. In 167 tumors tested from simplex cases with high-risk neuroblastomas, Mossé et al [2008] found that 14 had somatic ALK missense variants that were predicted to be activating. Of these 14 individuals with somatic ALK missense variants, germline DNA was available on nine. In one of those nine individuals the ALK pathogenic variant was identified in both germline and tumor DNA.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.