When a mutation overlaps multiple transcripts or genes, the GDC annotates all consequences in the all_effects column of the MAF file and in the CONSEQUENCE table on the Mutation Summary Page. One transcript is then selected as the default for detailed annotation and visualization where a single consequence is shown.
The default is chosen based on annotations from the Variant Effect Predictor (VEP), prioritizing the most severe consequence on the most impactful transcript biotype (See: selected annotation for the 'OneEffect'). The GDC also applies a curated transcript override file from MSKCC, which defines preferred transcripts for key genes, along with consideration for canonical and longest transcripts.
During GENCODE v36 updates in GDC Data Release 32 (DR 32), Some hotspot mutations may display a different default consequence annotation. For example, BRAF V600E is shown as BRAF V640E after DR32 because the curated BRAF transcript ENST00000288602 was updated by GENCODE with an addition of 40 amino acids at the N-terminus. Changes like this affect the default consequence annotations for all BRAF mutations and may similarly impact other genes with updated transcript models. Although the default annotation changed, users can still find V600E listed in the all_effects column in MAF files or the CONSEQUENCE table on the Mutation Summary Page alongside other transcript annotations.