Using data from the 100,000 Genomes Project to resolve conflicting interpretations of a recurrent TUBB2A mutation

Variant identification can be challenging for many clinically-relevant genes where highly similar DNA sequences are present elsewhere in the genome. In this study we focused on a recurrent TUBB2A variant (p.A248V) previously described to cause a neurodevelopmental disorder. Due to conflicting assessments in ClinVar and a surprisingly high frequency in some population databases, interpretation of this variant remained uncertain. Using 100K Genomes Project data, we analysed various technical parameters and identified a set of filters that can help distinguish genuine gene-conversion events from likely mapping artefacts.  Carefully designed PCR primers were used for variant validation. Similar results were seen for TUBB2B. (By Dr. Alistair T Pagnamenta, )

The first author Dr. Vassilis Ragoussis

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