Interpretation challenges of novel dual ‐class missense and splice‐impacting variant in POLR3A‐related late‐onset hereditary spastic ataxia

ConclusionThe novel dual ‐class c.3593A>C variant inPOLR3A causes an amino acid substitution and complex disruption of splicing. Our report supports the need to investigate variants near splice junctions for proper interpretation. Current interpretation guidelines need to address best practices for inclusion of predicted or measured transcriptional disruption pending functional activity or reliable transcript abundance estimates.

Source: Molecular Genetics & Genomic Medicine - June 28, 2020 Category: Genetics & Stem Cells Authors: Joel A. Morales ‐Rosado, Erica L. Macke, Margot A. Cousin, Gavin R. Oliver, Radhika Dhamija, Eric W. Klee Tags: ORIGINAL ARTICLE Source Type: research