DPYD and dihydropyrimidine dehydrogenase deficiency: Other DPYD variations previously reported as deleterious can explain 7.5% of the total DPD deficiencies (3/40 PM cases): c.2579delA (Q860fs, rs746991079), a frameshift variant resulting in protein truncation, previously isolated in individuals with DPD deficiency [43,44]; the Y211C allele, associated with consistent reduction of DPD activity (12.5–25% compared to wild-type) in an in-vitro assay using a recombinant mutant protein [34,45]; and the K259E allele, previously detected in a cohort of 5-FU treated patients undergoing toxicity [34].