---
title: How to recalculate variants in phase that are called separately?
description: In the rare case variants, such as MNPs (multi-nucleotide polymorphisms) delinses, are split into smaller atomic SNVs (single nucleotide variants) or INDELs (insertions and deletions), they may need t
---

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# How to recalculate variants in phase that are called separately?

In the rare case variants, such as MNPs (multi-nucleotide polymorphisms) delinses, are split into smaller atomic SNVs (single nucleotide variants) or INDELs (insertions and deletions), they may need to be recalculated into a single MNP. This process is important for accurate classification, especially when determining if two variants are in [phase](https://docs.varsome.com/en/phasing?hsLang=en) or are independent. This article explains how to recalculate split variants into a single MNP using VarSome Clinical, with a detailed example from a clinical case.

---

### **Case example: ENG gene variants**

Consider a case where we have two variants in the **ENG** gene, and the end user is seeking confirmation about whether these two variants are in phase and should be analyzed together or if they are independent in the **hg19** reference genome:

- **Variant 1:** [NM\_001114753.3:c.466\_471del](https://varsome.com/variant/hg19/NM_001114753.3%3Ac.466_471del?annotation-mode=germline)(p.Ile156\_Thr157del)
- **Variant 2:** [NM\_001114753.3:c.445\_458del](https://varsome.com/variant/hg19/NM_001114753.3%3Ac.445_458del?annotation-mode=germline)(p.Trp149GlyfsTer8)

### **Step 1: Identifying other potential involved variants**

Before determining whether the variants are in phase, it is useful to check for other variants in the genomic neighborhood that might be involved. Here’s how to identify them:

1. **Nearby Variants card:** In VarSome Clinical, navigate to the [**Nearby Variants**](https://docs.varsome.com/en/clinical-cards?hsLang=en) section in the clinical card for the selected variant. This will display variants in the genomic neighborhood of your variant.
2. **Not affected by sample filters:** This list will not be affected by any filters applied to the sample, so it provides a comprehensive look at other variants in the area.
3. **Check PGT and PID for nearby variants:** By reviewing these nearby variants, you can assess if any of them share the same **PGT** and **PID** attributes, suggesting that they might also be in phase or linked to the variants in question.

### **Step 2: Determine if the variants are in phase**

To determine if the two variants are in phase, follow these steps within VarSome Clinical:

1. **Search for VCF attributes PGT and PID:**
   
     - **PGT (Physical Phasing Haplotype Information):** Describes how the alternate alleles are phased relative to one another (e.g., 0|1 or 1|0).
     - **PID (Physical Phasing ID Information):** A unique ID within a sample that connects records within a phasing group.
2. **Comparing PGT and PID:** In VarSome Clinical, these attributes will appear in the variant details (as shown in the example image below). Compare the **PGT** and **PID** values for both variants.
   
   [![](https://docs.varsome.com/hs-fs/hubfs/image-png-Feb-18-2025-05-29-36-1724-PM.png?width=688&height=133&name=image-png-Feb-18-2025-05-29-36-1724-PM.png)](https://docs.varsome.com/hubfs/image-png-Feb-18-2025-05-29-36-1724-PM.png?hsLang=en)
   
   **Key rule:** If two variants share the same **PGT** and **PID**, they are not independent, meaning they are on the same haplotype and therefore in phase. This means the variants should not be analyzed separately.
3. **Conclusion:** In this case, if the **PGT** and **PID** for both variants are identical, they are in phase. As a result, they should be recalculated into a single variant.

### **Step 3: Recalculate the variant**

Once you determine that the variants are in phase, you need to recalculate the two split variants into a single MNP. Here’s how to do that:

1. **Reference sequence:** Start with the reference sequence where the two variants occur:
   
   `GGTGATGGGGCCCCTCTCAGCTGCCCA`

     - **Variant 1 (c.466\_471del)** is the **underlined** first 6 nucleotides.
     - **Variant 2 (c.445\_458del)** is the second **underlined** segment of 14 nucleotides.
2. **Resulting sequence after deletions:** These two deletions occur at the same time, which means the combined result is the deletion of the bases from both variants. The resulting sequence will be:
   
   `GGGGCCC`
3. **Formulate the query:** Use the resulting sequence to create a new VarSome query:
   
   `chr9:130588841:GGTGATGGGGCCCCTCTCAGCTGCCCA:GGGGCCC`

   This will give you the [merged variant](https://varsome.com/variant/hg19/chr9%3A130588841%3AGGTGATGGGGCCCCTCTCAGCTGCCCA%3AGGGGCCC?annotation-mode=germline).
4. **Recalculated variant:** The recalculated variant is now:
   
   `ENG(NM_001114753.3):c.445_469delinsGGGCC p.(Trp149GlyfsTer6)`

   This is the single MNP that combines the two original variants.

Using the **PGT** and **PID** attributes in VarSome Clinical, you can easily determine if variants are in phase and merge them accordingly. The recalculation process helps ensure a more accurate analysis of genetic variants.

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