Targeted callers

SMN Caller

Variants in the SMN1 gene are only prioritised using a targeted caller. The SMN Caller infers copy numbers of intact SMN1, intact SMN2 and SMN2 with deletion of exon 7 and 8. To calculate the SMN1 copy number, the caller uses eight predefined differentiating sites in exons 7 and 8 of SMN1 and SMN2. The caller selects differentiating sites at positions that have sequence differences between SMN1 and SMN2 where calling the SMN1 copy number is most likely to be correct based on sequencing data from the 1000 Genomes Project. For each differentiating site, the SMN1-specific and SMN2-specific alleles are counted in reads mapping to either SMN1 or the homologous region in SMN2. Further details regarding the SMN Caller can be found in the user guide: SMA Calling User Guide and the publication: Spinal muscular atrophy diagnosis and carrier screening from genome sequencing data.

The case will be marked as having clinically relevant SMN1 findings if inferred copy number of intact SMN1 is zero. The inferred copy numbers of intact SMN2 and SMN2 with deleted exons 7 and 8 are not used for prioritisation, but are available during interpretation of the case.