> 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/illumina-ffpe-dna-prep-with-exome-2.5/additional-information/germline-variants.md). # Germline variants To explore germline variants that might play a role in tumor analysis, it is recommended to run an additional analysis, the[ DRAGEN Germline pipeline](https://help.dragen.illumina.com/product-guides/dragen-v4.3/dragen-recipes/germline-wes), on the normal sample. The highest performance for the detection of both somatic and germline variants is achieved by implementing the Tumor/Normal (T/N) Somatic Variant Calling workflow and additionally the dedicated Germline pipeline on the Normal sample. ### How It Works In somatic T/N analysis, DRAGEN uses a subtraction model for small variants (SNVs and indels). The matched normal provides a more reliable indicator of somatic variants than comparisons with public databases. Because the T/N model identifies variants where there are no (or very few) alternate-supporting reads in the normal sample, germline variants (present in both the tumor and normal sampeles) are intentionally suppressed from the somatic VCF output. To recover germline variants, a dedicated germline pipeline should be run on the normal sample. This caller uses a different statistical model optimized for diploid genotyping, evaluating evidence for heterozygous (0/1) and homozygous alternate (1/1) calls at expected allele fractions of \~50% and \~100%, respectively. It also produces calibrated quality metrics (GQ, PL) expected by downstream clinical interpretation workflows. Running both the somatic pipeline on the tumor-normal pair and the germline pipeline on the normal sample ensures that each variant type is called by the model best suited to detect it. The resulting somatic and germline VCFs are output from separate analyses and can be used independently or merged as needed for reporting. DRAGEN software development is ongoing to streamline these two analyses. --- # Agent Instructions This documentation is published with GitBook. GitBook is the documentation platform designed so that both humans and AI agents can read, navigate, and reason over technical content effectively. Learn more at gitbook.com. ## 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, and the optional `goal` query parameter: ``` GET https://help.connected.illumina.com/illumina-ffpe-dna-prep-with-exome-2.5/additional-information/germline-variants.md?ask=&goal= ``` `ask` is the immediate question: it should be specific, self-contained, and written in natural language. `goal` is optional and describes the broader end goal you are ultimately trying to accomplish on behalf of the user. GitBook uses it to tailor the answer towards what is most useful for that goal. 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.