Spinal Muscular Atrophy Calling

Disruption of all copies of the SMN1 gene in an individual causes spinal muscular atrophy (SMA). SMN1 has a high identity paralog, SMN2. SMN2 differs only in approximately 10 SNVs and small indels. For example, hg19 chr5:70247773 C->T affects splicing and largely disrupts the production of functional SMN protein from SMN2. Due to the high-similarity duplication combined with common-copy number variation, standard whole-genome sequencing (WGS) analysis does not produce complete variant calling results for SMN. Since 95% of SMA cases result from the absence of the functional C (SMN1) allele in any copy of SMN¹, a targeted calling solution can be effective in detecting SMA.

DRAGEN offers the following two independent components to detect SMA status from WGS data.

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ExpansionHunter

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SMN Caller

In addition to SMA status, the SMN Caller reports SMN1/SMN2 copy numbers and identifies SMA carrier status.

¹Wirth B. An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA). Human Mutation. 2000;15(3):228-237. doi:10.1002/(sici)1098-1004(200003)15:3<228::aid-humu3>3.0.co;2-9