> For the complete documentation index, see [llms.txt](https://help.connected.illumina.com/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://help.connected.illumina.com/dragen-5-base/run-analysis-setup/ica-analysis-setup/dragen-germline-whole-genome.md).

# DRAGEN Germline Whole Genome

<figure><img src="/files/URnaemzfUiRKUR4DZqRJ" alt=""><figcaption></figcaption></figure>

Select the DRAGEN\_Germline\_Whole\_Genome\_4-5-4 Pipeline.

**WARNING**: Deviation from these instructions (including adding additional options) may cause pipeline failure.

1. Select the necessary input files for the run, including sample inputs (.fastq, .fastq.ora, .bam, or .cram files), and a custom DRAGEN Reference Genome.
   1. Note: 5-base is compatible with any methyl\_cg references. A graph reference is recommended for Germline and non-graph is the recommendation for Somatic.<br>

      <figure><img src="/files/qd2ZhWzTiBDI338BogcO" alt=""><figcaption></figcaption></figure>
2. To Enable Methylation Aware Algorithms, select "True" for Enable 5-Base Methylation-Aware Algorithms.<br>

   <figure><img src="/files/zU9A6pfSzXLBv5TPyqBd" alt=""><figcaption></figcaption></figure>
3. (Optional) To perform Small Variant Calling, set Enable Variant Caller to "True" and Emit Ref Confidence to "GVCF".<br>

   <figure><img src="/files/KWj30QWoVySPFwDRJWPs" alt=""><figcaption></figcaption></figure>
4. If no Small Variant Calling is needed, set Enable Variant Caller to "False" and click the "X" next to Emit Ref Confidence.\ <br>

   <figure><img src="/files/xNCuELN3DXOiAolmxDR7" alt=""><figcaption></figcaption></figure>
5. For Report Methylation at Variant Positions, select "default".<br>

   <figure><img src="/files/ODlTYIrh9pMAn9hsY2uX" alt=""><figcaption></figcaption></figure>
6. (Optional) To perform CNV calling, set Enable CNV Calling to "True". Optionally turn on allele-specific CNV Calling.<br>

   <figure><img src="/files/DyLCvIab7gEflwE9w9ma" alt=""><figcaption></figcaption></figure>
7. (Optional) To Enable SV Calling, select "True".
   1. <mark style="color:blue;">**NOTE**</mark>: While SV Calling is validated as a stand alone option for DRAGEN Germline, they also improve CNV calling accuracy, and thus are recommended when running CNV Calling. .

      <figure><img src="/files/4EUro3cJJL9q8TVdVFlD" alt=""><figcaption></figcaption></figure>
8. In the Additional Options section:
   1. (Optional) Check "Enable Variant Annotations" to turn on Nirvana Variant Annotation.
   2. (Optional) If downsampling is required, under Additional DRAGEN Commandline Argument, add `--enable-fractional-down-sampler=true --down-sampler-normal-subsample=$Fraction`, where $Fraction is a value between 0 and 1 representing the proportion of reads to keep.
   3. (Optional) Under Additional DRAGEN Commandline Arguments, add `--gc-metrics-enable=true` to enable GC metrics.
9. Start the analysis.


---

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