The proposal suggests to extend the HGVS recommendations to improve the description of variants affecting circular DNA molecules by;
For deletions the current recommendations state: the “position(s)_deleted” should be listed from 5’ to 3’, e.g. 123_126 not 126_123. As a consequence a deletion involving the start/end of a mitochondrial reference sequence can not be described as NC_012920.1:m.16563_13del. Adding the exception simplifies the description of rearrangements involving both the last and first nucleotides of circular DNA molecules. The suggestion to use the “o.” prefix should help to discriminate circular from non-circular genomic reference sequences. While less relevant for human genetics, circular DNA sequences are common in nature (e.g. viruses, bacterial genomes, plasmids, chloroplast). Allowing the “o.” prefix simplifies recognition of circular reference sequences, simplifies the description of deletions/duplications involving both the last and first nucleotides and promotes the wider implementation of HGVS nomenclature. The “o.” prefix will also help computational tools to check correct variant descriptions.