Spinal Muscular Atrophy Calling

Disruption of all copies of the SMN1 gene in an individual causes spinal muscular atrophy (SMA). SMN1 has a very high identity paralog, SMN2, with differs only in approximately 10 SNVs and small indels. One of these (hg19 chr5:70247773 C->T) affects splicing and largely disrupts the production of functional SMN protein from SMN2. Standard WGS analysis does not produce complete variant calling results for SMN due to this high-similarity duplication combined with common copy-number variation. However, approximately 95% of SMA cases can be detected by determining the absence of the functional C (SMN1) allele in any copy of SMN.

DRAGEN SMA calling uses sequence-graph realignment to align reads to a single reference representing SMN1 and SMN2. In addition to the standard diploid genotype call, DRAGEN uses a direct statistical test to check for presence of any C allele. If no C allele is detected, the sample is called affected, otherwise unaffected.

SMA calling is only supported for human whole-genome sequencing samples in PCR-free libraries.