Marko Velimirovic MD MMSc

🧬 Ever wondered what “VAF = 42%” means in your NGS report? Let’s decode it in simple terms 👇 When we sequence DNA, we get thousands of short fragments called reads. Some reads are 🧩 normal, others carry a 🧬 mutation. 👉 Variant Allele Frequency (VAF) tells us what fraction of all those reads carry the mutation. 📊 Example: Out of 100 reads, if 42 show the mutation → VAF = 42% Think of it like a mini election inside your DNA - 42% votes for the mutant candidate 🗳️ 💡 How to interpret it: 🔹 ~50% → One of two alleles mutated → Heterozygous germline variant 🔹 ~100% → Both alleles mutated → Homozygous germline variant 🔹 5–30% → Found only in a subset of tumor cells → Somatic or subclonal mutation 🔹 >90% → Often indicates Loss of Heterozygosity (LOH) ⚠️ But remember: 🚫 VAF ≠ tumor purity 🚫 High VAF ≠ “more dangerous” 🚫 Low VAF ≠ “insignificant” VAF only shows how frequent a mutation appears in the reads - not whether it’s harmful or benign. 🧠 Pro tip: Always interpret VAF along with: 🔸 Tumor purity 🔸 Copy-number changes 🔸 Zygosity 🔸 Subclonal structure ✨ In short: VAF is your mutation’s vote share in the sequencing data 🗳️ It’s a clue to where the mutation comes from - not how bad it is. 🔖 Save this for your next NGS report review! #OncoTwitter #CancerGenomics #NGS #MedTwitter #oncology #cancer #PrecisionOncology @OncoAlert @ASCO @myESMO @ESMO_Open @NCICancer