The value of primary transcripts to the clinical and non-clinical
genomics community: survey results and roadmap for improvements.
Variant interpretation is dependent on transcript annotation and remains
time consuming and challenging. There are major obstacles for historical
data reuse and for interpretation of new variants. First, both RefSeq
and Ensembl/GENCODE produce transcript sets in common use, but there is
currently no easy way to translate between the two. Second, the
resources often used for variant interpretation (e.g. ClinVar, gnomAD,
UniProt) do not use the same transcript set, nor default transcript or
protein sequence. Ensembl ran a survey in 2018 to assay attitudes to
choosing one default transcript per locus, and to gather data on
reference sequences used by the scientific community. This was
publicised on the Ensembl and UCSC genome browsers, by email and on
social media. We had 788 respondents. Here we report our results and
roadmap to create an effective default set of transcripts for resources,
and for reporting interpretation of clinical variants.