# Classification & Risk Stratification Prediction
{% hint style="info" %}
Classification & Risk Stratification Prediction is available for cases created using Connected Insights v5.1+.
{% endhint %}
## Overview
If the case disease is Acute Myeloid Leukemia or a subtype, Classification & Risk Stratification Prediction is provided on the [Overview Tab](/connected-insights/interpret-and-report/cm-overview-tab.md).
APL with PML::RARA fusion prediction with decision tree
Classification and risk stratification predictions are based on [WHO 2022](https://tumourclassification.iarc.who.int/chapters/63) and [ELN 2022](https://pubmed.ncbi.nlm.nih.gov/35797463/) acute myeloid leukemia guidelines, respectively, focusing on *Acute myeloid leukemia with defining genetic abnormalities.*
Select a box to review how the evaluation was performed. For more information, refer to [Decision Trees](#decision-trees) below.
## Reporting
The report interpretation summary can be generated from the prediction results by clicking **Report**.
Generated interpretation summary text
## Decision Trees
***
### APL with PML::RARA fusion
#### **Classification**
* [Blast count](/connected-insights/interpret-and-report/cm-cases-details.md) % ≥ 10
* [History of cytotoxic therapy exposure](/connected-insights/interpret-and-report/cm-cases-details.md) = No
* Any of the following:
* Detection of PML::RARA fusion with ≥ 2 split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of t(15;17)(q24;q21) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
If the above is met, the classification is predicted to be APL with PML::RARA fusion.
#### **Risk Stratification**
* Detection of TP53 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filter = PASS
* Small variant
* Somatic origin (origin = somatic or unknown)
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then Intermediate.
***
### AML with RUNX1::RUNX1T1 fusion
#### **Classification**
* [Blast count](/connected-insights/interpret-and-report/cm-cases-details.md) % ≥ 10
* [History of cytotoxic therapy exposure](/connected-insights/interpret-and-report/cm-cases-details.md) = No
* Any of the following:
* Detection of RUNX1::RUNX1T1 fusion with ≥ 2 split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of t(8;21)(q21.3;q22.1) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
{% hint style="info" %}
The guideline specifies an outdated band 8q22 for RUNX1T1. It is now 8q21.3.
{% endhint %}
If the above is met, the classification is predicted to be AML with RUNX1::RUNX1T1 fusion.
#### **Risk Stratification**
* Detection of TP53 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filter = PASS
* Small variant
* Somatic origin (origin = somatic or unknown)
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then Favorable.
***
### AML with CBFB::MYH11 fusion
#### **Classification**
* [Blast count](/connected-insights/interpret-and-report/cm-cases-details.md) % ≥ 10
* [History of cytotoxic therapy exposure](/connected-insights/interpret-and-report/cm-cases-details.md) = No
* Any of the following:
* Detection of CBFB::MYH11 fusion with ≥ 2 split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of inv(16)(p13.1q22.1) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of t(16;16)(p13.1;q22.1) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
If the above is met, the classification is predicted to be AML with CBFB::MYH11 fusion.
#### **Risk Stratification**
* Detection of TP53 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filter = PASS
* Small variant
* Somatic origin (origin = somatic or unknown)
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then Favorable.
***
### AML with DEK::NUP214 fusion
#### **Classification**
* [Blast count](/connected-insights/interpret-and-report/cm-cases-details.md) % ≥ 10
* [History of cytotoxic therapy exposure](/connected-insights/interpret-and-report/cm-cases-details.md) = No
* Any of the following:
* Detection of DEK::NUP214 fusion with ≥ 2 split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of t(6;9)(p22.3;q34.1) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
If the above is met, the classification is predicted to be AML with DEK::NUP214 fusion.
#### **Risk Stratification**
Adverse
***
### AML with RBM15::MRTFA fusion
#### **Classification**
* [Blast count](/connected-insights/interpret-and-report/cm-cases-details.md) % ≥ 10
* [History of cytotoxic therapy exposure](/connected-insights/interpret-and-report/cm-cases-details.md) = No
* Any of the following:
* Detection of RBM15::MRTFA fusion with ≥ 2 split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of t(1;22)(p13.3;q13.1) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
If the above is met, the classification is predicted to be AML with RBM15::MRTFA fusion.
#### **Risk Stratification**
* Detection of TP53 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filter = PASS
* Small variant
* Somatic origin (origin = somatic or unknown)
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then Intermediate.
***
### AML with BCR::ABL1 fusion
#### **Classification**
* [Blast count](/connected-insights/interpret-and-report/cm-cases-details.md) % ≥ 20
* [History of cytotoxic therapy exposure](/connected-insights/interpret-and-report/cm-cases-details.md) = No
* Any of the following:
* Detection of BCR::ABL1 fusion with ≥ 2 split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of t(9;22)(q34.1;q11.2) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
If the above is met, the classification is predicted to be AML with BCR::ABL1 fusion.
#### **Risk Stratification**
Adverse
***
### AML with KMT2A rearrangement
#### **Classification**
* [Blast count](/connected-insights/interpret-and-report/cm-cases-details.md) % ≥ 10
* [History of cytotoxic therapy exposure](/connected-insights/interpret-and-report/cm-cases-details.md) = No
* Detection of KMT2A structural variant with VCF filter = PASS in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
If the above is met, the classification is predicted to be AML with KMT2A rearrangement.
#### **Risk Stratification**
* Detection of TP53 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filter = PASS
* Small variant
* Somatic origin (origin = somatic or unknown)
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then continue below.
* Any of the following:
* Detection of MLLT3::KMT2A / KMT2A::MLLT3 with VCF filter = PASS in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of t(9;11)(p21.3;q23.3) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of KMT2A partial tandem duplication with VCF filter = PASS in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
If the above is met, the risk stratification is predicted to be Intermediate. If not, then Adverse.
***
### AML with MECOM rearrangement
#### **Classification**
* [Blast count](/connected-insights/interpret-and-report/cm-cases-details.md) % ≥ 10
* [History of cytotoxic therapy exposure](/connected-insights/interpret-and-report/cm-cases-details.md) = No
* Any of the following:
* Detection of MECOM, including upstream region, structural variant with VCF filter = PASS in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of inv(3)(q21.3q26.2) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of t(3;3)(q21;q26) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of t(3;21)(q26.2;q22) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of t(3;12)(q26.2;p13) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
If the above is met, the classification is predicted to be AML with MECOM rearragement.
#### **Risk Stratification**
Adverse
***
### AML with NUP98 rearrangement
#### **Classification**
* [Blast count](/connected-insights/interpret-and-report/cm-cases-details.md) % ≥ 10
* [History of cytotoxic therapy exposure](/connected-insights/interpret-and-report/cm-cases-details.md) = No
* Any of the following:
* Detection of NUP98 structural variant with VCF filter = PASS in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of t(5;11)(q35.2;p15.4) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of t(11;12)(p15.4;p13.3) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
If the above is met, the classification is predicted to be AML with NUP98 rearrangement.
#### **Risk Stratification**
* Detection of TP53 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filter = PASS
* Small variant
* Somatic origin (origin = somatic or unknown)
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then Intermediate.
***
### AML with NPM1 mutation
#### **Classification**
* [Blast count](/connected-insights/interpret-and-report/cm-cases-details.md) % ≥ 10
* [History of cytotoxic therapy exposure](/connected-insights/interpret-and-report/cm-cases-details.md) = No
* Detection of NPM1 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* Allele depth ≥ 2
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
If the above is met, the classification is predicted to be AML with NPM1 mutation.
#### **Risk Stratification**
* Any of the following:
* Detection of TP53 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filter = PASS
* Small variant
* Somatic origin (origin = somatic or unknown)
* Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
* VAF ≥ 0.10 (10%)
* Detection of DEK::NUP214 fusion with ≥ 2 split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of t(6;9)(p22.3;q34.1) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of KMT2A structural variant without MLLT3 fusion partner with VCF filter = PASS in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of BCR::ABL1 fusion with ≥ 2 split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of t(9;22)(q34.1;q11.2) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of KAT6A::CREBBP fusion with ≥ 2 split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of t(8;16)(p11.2;p13.3) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of MECOM, including upstream region, structural variant with VCF filter = PASS in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of inv(3)(q21.3q26.2) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of t(3;3)(q21;q26) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of t(3;21)(q26.2;q22) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of t(3;12)(q26.2;p13) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of monosomy 5 in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype), or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with VCF filters = PASS
* Detection of 5q deletion in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype), or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with length ≥ 5 Mbp and VCF filters = PASS
* Detection of monosomy 7 in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype), or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with VCF filters = PASS
* Detection of monosomy 17 in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype), or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with VCF filters = PASS
* Detection of 17p deletion in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype), or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with length ≥ 5 Mbp and VCF filters = PASS
* Detection of [complex karyotype](#complex-karyotype) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype) or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of [monosomal karyotype](#monosomal-karyotype) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype) or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
If the above is met, the risk stratification is predicted to be Adverse. If not, then continue below.
* Detection of FLT3 internal tandem duplication with ≥ 2 allele depth or split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
If the above is met, the risk stratification is predicted to be Intermediate. If not, then Favorable.
***
### AML with CEBPA mutation
#### **Classification**
* None of the classifications above should be met.
* [Blast count](/connected-insights/interpret-and-report/cm-cases-details.md) % ≥ 20
* [History of cytotoxic therapy exposure](/connected-insights/interpret-and-report/cm-cases-details.md) = No
* Any of the following:
* Detection of **2 CEBPA variants** in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Detection of CEBPA variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Located in the bZIP domain
{% hint style="warning" %}
The guideline requires biallelic mutations, whereas the evaluation simply checks for 2 due to lack of cis/trans information.
{% endhint %}
If the above is met, the classification is predicted to be AML with CEBPA mutation.
#### **Risk Stratification**
* Detection of TP53 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Somatic origin (origin = somatic or unknown)
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then continue below.
* Detection of CEBPA variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* In-frame (not a frameshift variant)
If the above is met, the risk stratification is predicted to be Favorable. If not, then Intermediate.
***
### AML with other defined genetic alterations
#### **Classification**
* None of the classifications above should be met.
* [Blast count](/connected-insights/interpret-and-report/cm-cases-details.md) % ≥ 20
* [History of cytotoxic therapy exposure](/connected-insights/interpret-and-report/cm-cases-details.md) = No
* Any of the following:
* Detection of CBFA2T3::GLIS2 fusion with ≥ 2 split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of inv(16)(p13q24) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of KAT6A::CREBBP fusion with ≥ 2 split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of t(8;16)(p11.2;p13.3) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of FUS::ERG fusion with ≥ 2 split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of t(16;21)(p11;q22) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of MNX1::ETV6 fusion with ≥ 2 split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of t(7;12)(q36;p13) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of NPM1::MLF1 fusion with ≥ 2 split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of t(3;5)(q25;q35) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
If the above is met, the classification is predicted to be AML with other defined genetic alterations.
#### **Risk Stratification**
* Detection of TP53 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Somatic origin (origin = somatic or unknown)
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then continue below.
* Any of the following:
* Detection of KAT6A::CREBBP fusion with ≥ 2 split reads and paired reads in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of t(8;16)(p11.2;p13.3) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
If the above is met, the risk stratification is predicted to be Adverse. If not, then Intermediate.
***
### AML, myelodysplasia-related
#### **Classification**
* None of the classifications above should be met.
* [Blast count](/connected-insights/interpret-and-report/cm-cases-details.md) % ≥ 20
* [History of cytotoxic therapy exposure](/connected-insights/interpret-and-report/cm-cases-details.md) = No
* Any of the following:
* [History of myelodysplastic syndrome](/connected-insights/interpret-and-report/cm-cases-details.md) = Yes
* Both of the following:
* [History of myelodysplastic syndrome](/connected-insights/interpret-and-report/cm-cases-details.md) = Yes
* [History of myeloproliferative neoplasm](/connected-insights/interpret-and-report/cm-cases-details.md) = Yes
* Detection of [complex karyotype](#complex-karyotype) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype) or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of 5q deletion in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype), or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with length ≥ 5 Mbp and VCF filters = PASS
* Detection of monosomy 7 in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype) or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with VCF filters = PASS
* Detection of 11q deletion in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype), or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with length ≥ 5 Mbp and VCF filters = PASS
* Detection of 12p deletion in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype), or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with length ≥ 5 Mbp and VCF filters = PASS
* Detection of monosomy 13 in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype), or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with VCF filters = PASS
* Detection of 17p deletion in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype), or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with length ≥ 5 Mbp and VCF filters = PASS
* Detection of isochromosome 17q in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of idic(X)(q13) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype)
* Detection of ASXL1 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Detection of BCOR variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Detection of EZH2 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Detection of SF3B1 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Detection of SRSF2 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Detection of STAG2 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Detection of U2AF1 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Detection of ZRSR2 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
If the above is met, the classification is predicted to be AML, myelodysplasia-related.
#### **Risk Stratification**
Any of the following:
* Detection of TP53 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* Small variant
* Somatic origin (origin = somatic or unknown)
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* VAF ≥ 0.10 (10%)
* Detection of monosomy 5 in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype), or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with VCF filters = PASS
* Detection of 5q deletion in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype), or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with length ≥ 5 Mbp and VCF filters = PASS
* Detection of monosomy 7 in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype), or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with VCF filters = PASS
* Detection of monosomy 17 in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype), or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with VCF filters = PASS
* Detection of 17p deletion in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype), or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with length ≥ 5 Mbp and VCF filters = PASS
* Detection of [complex karyotype](#complex-karyotype) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype) or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of [monosomal karyotype](#monosomal-karyotype) in the [User Determined Karyotype](/connected-insights/interpret-and-report/cm-overview-tab.md#user-determined-karyotype) or [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md)
* Detection of ASXL1 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Detection of BCOR variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Detection of EZH2 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Detection of SF3B1 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Detection of SRSF2 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Detection of STAG2 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Detection of U2AF1 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
* Detection of ZRSR2 variant in the [Variants Tab](/connected-insights/interpret-and-report/inter-variant-grid.md) with the following characteristics:
* VCF filters = PASS
* Small variant
* Oncogenic or likely oncogenic (as indicated by a knowledge base [biological classification](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-biological-classification-assertions.md) or [oncogenicity prediction](/connected-insights/interpret-and-report/viewdetails-introduction/viewdetails-oncogenicity-prediction.md))
If the above is met, the risk stratification is predicted to be Adverse. If not, then Intermediate.
***
### Definitions
#### Complex Karyotype
According to WHO/ISCN: ≥ 3 abnormalities, where abnormalities are counted as follows:
* Only clonal abnormalities are counted; abnormalities present in only 1 metaphase are ignored.
* Numerical gains and losses, simple and complex balanced translocations, unbalanced aberrations involving one chromosome, as well as multiplication of a complete chromosome set are counted as one abnormality.
* Unbalanced aberrations involving two or more chromosomes, tetrasomy of same chromosome, triplication or quadruplication, as well as isoderivative chromosomes, are counted as 2 abnormalities.
* Constitutional abnormalities are not counted.
* In case of multiple clones (subclones or independent clones), chromosome abnormalities in each clone/subclone are counted separately and the number of chromosomal abnormalities is defined by the clone with the highest abnormalities.
* For composite karyotypes, clonal chromosomal aberrations are counted in metaphases with the highest number of abnormalities.
We consider the following when counting abnormalities:
* Recurrent SVs
* One CNV ≥ 5 Mbp per chromosome arm
#### Monosomal Karyotype
According to ELN: Presence of two or more distinct monosomies (excluding loss of X or Y), or one single autosomal monosomy in combination with at least one structural chromosome abnormality (excluding core-binding factor AML).
---
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