Documentation / Computational Predictors / DANN
DANN Score Interpretation for Genetic Variants
DANN scores range from 0 to 1. Scores at or above 0.95 are labelled damaging, while 0.5 to 0.95 remains a broad ambiguous interval. Folklore displays DANN for review but does not use it to assign PP3 or BP4.
What the Score Represents
DANN is a neural-network score derived from genomic annotations. It can score single nucleotide variants in coding and non-coding regions, including positions where missense-specific predictors do not apply.
The 0.95 Threshold
DANN scores range from 0 to 1, with higher scores indicating a greater likelihood of pathogenicity.
| Score Range | Interpretation |
|---|---|
| >= 0.95 | Predicted damaging with high confidence |
| 0.5 -- 0.95 | Ambiguous range -- insufficient confidence for a clear prediction |
| < 0.5 | Predicted benign |
Strengths and Limitations
DANN's primary strength is breadth: it can score any single nucleotide variant in the genome, not just missense variants in coding regions. This makes it useful as a reference for intronic, synonymous, and UTR variants where protein-specific tools like SIFT or AlphaMissense are not applicable.
The main limitation is its wide ambiguous range (0.5 to 0.95), which means many variants receive scores that are neither clearly damaging nor clearly benign. The binary threshold approach may also miss nuanced pathogenicity signals.
Role in Folklore
DANN scores are displayed in the variant detail view as additional clinical context. They do not contribute to PP3 or BP4 ACMG criteria. The formal classification uses BayesDel_noAF with ClinGen SVI calibrated thresholds. See BayesDel thresholds for details.
Reference: Quang D, Chen Y, Xie X. Bioinformatics. 2015;31(5):761-763. PMID: 25338716