Junction Preserving Annotation

Background

When a variant can be moved (due to alignment) across junctions (e.g. start, stop or splice site), the annotation may vary depending on which exact alignment was used. For example, a left-aligned deletion that effects the splice acceptor site, upon right-alignment, may become an exon variant.

Note that:

• When right-aligned the variant starts at the first base of the exon (as pictured).
• When left-aligned the variant can be shifted two base pairs and starts at a splice acceptor site.

From the point of view of the translation mechinary, the important question is whether the sequence that identifies a junction is preserved, regardless of the variant position. In the case of the deletion above, we believe that the variant is more accurately characterized as an inframe_deletion not a splice_acceptor_variant as splice acceptor sequence AG is unaffected.

When faced with such variants, we will assign junction disrupting consequnces only if the variant cannot be shifted out of the junction.

Implementation

By default and convention, the left-aligned variant is annotated. If the variant overlaps a junction (as judged by consequences), it is right-aligned and annotated. If both alignment produces junction disruption, the left-aligned annotation is reported. If however, only one of the alignment causes junction disruption but not the other, the non-junction-disrupting annotation is reported.

note

This only effects transcript annotations. Supplementary annotations are reported on the left-aligned variant and HGVS notations are calculated on right-aligned variant.