# Known Limitations ### Functionality * This software solution will only work with the 5-base Library Prep kit * DRAGEN Methylation can be run on 5-base data, but it will produce lower alignment and no variant calls * Somatic Tumor/Normal analysis is not supported in Enrichment workflows * CNV analysis is not supported in Enrichment workflows * SV results are turned on to improve CNV calling accuracy, but these results are not verified or supported ### Performance * 5-base alignment may underperform on genomes with significant non-CpG methylation levels * M-bias calculations are inaccurate for R2 for cfDNA samples when using default settings * Recommendation is to add `--mbias-report-include-overlaps=true` for this use case * Integrated downsampling is not functional for DRAGEN Enrichment * If downsampling is required, run with the fractional downsampler in the DRAGEN FASTQ Toolkit ### Variant Calling * Any additional variant callers are not supported, and any data generated by them has not been validated * Variant calling is only currently supported for human reference genomes * If required, non-human reference genomes must be uploaded in a v11 file format. These will not produce variant calls that the Illumina team supports. The following error will be displayed in ICA, but the run will complete: `WARNING: --methylation-conversion=illumina is only supported on human references.` --- # Agent Instructions: Querying This Documentation If you need additional information that is not directly available in this page, you can query the documentation dynamically by asking a question. Perform an HTTP GET request on the current page URL with the `ask` query parameter: ``` GET https://help.connected.illumina.com/dragen-5-base/additional-information/known-limitations.md?ask= ``` The question should be specific, self-contained, and written in natural language. The response will contain a direct answer to the question and relevant excerpts and sources from the documentation. Use this mechanism when the answer is not explicitly present in the current page, you need clarification or additional context, or you want to retrieve related documentation sections.