Thrombocytopenia 2 and Predisposition to Myeloid Malignancies via the ANKRD26 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 3143 | ANKRD26 | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
Clinical Features
Inherited thrombocytopenias (IT) comprise a heterogeneous group of disorders characterized by platelet counts below the lower limit of normal, below 150,000/µL (150 x 109/L) in adults. Bleeding manifestations of thrombocytopenia range from mild to severe and may include excessive bruising (purpura), petechiae, prolonged bleeding from cuts or from surgical procedures, spontaneous nose bleeds, and in women, heavy menstrual flows. About half of ITs are syndromic disorders characterized by other physical and neurological anomalies, or immunodeficiencies (Balduini et al. 2013. PubMed ID: 23397552). Over 30 genes are known to be associated with ITs. Pathogenic variants in known genes are found in only about 50% of cases (Kunishima and Saito. 2006. PubMed ID: 16169642; Noris and Pecci. 2017. PubMed ID: 29222283). Noris and Pecci divide ITs into three groups: forms characterized by only platelet deficiencies, syndromic ITs with additional congenital defects, and ITs associated with increased risk of developing additional disease such as myelodysplastic syndrome (MDS) and acute leukemia (AL). For additional information regarding inherited hematologic malignancies, see Churpek et al. 2013. PubMed ID: 22691122; Furutani and Shimamura. 2017. PubMed ID: 28297620. It is important to distinguish ITs from immune/idiopathic thrombocytopenias (ITP) in order to inform clinical management and identify potential at risk family members.
ANKRD26-associated thrombocytopenia 2 (THC2) is characterized by moderately low platelet counts (family averages = 40-60/nl) (Savoia et al. 1999. PubMed ID:10521306; Drachman et al. 2000. PubMed ID:10891439). Platelets are of normal size. Patients often bruise easily and have moderate bleeding problems. Thrombopoietin levels are mildly elevated. Pathogenic variants in ANKRD26 are associated with predisposition to MDS and AML; up to a 30 fold increase in the frequency of MDS and AML has been reported in patients with ANKRD26 pathogenic variants (Noris et al. 2011. PubMed ID:21467542; Noris et al. 2013. PubMed ID:24030261; Marquez et al. 2014. PubMed ID:24628296).
Genetics
THC2 is an autosomal dominant form of thrombocytopenia that has been attributed to variants in the MASTL (Gandhi et al. 2003. PubMed ID: 12890928) and ABCD5 (Punzo et al. 2010. PubMed ID: 20626622) genes. More recently, THC2 has been attributed to variants in the ANKRD26 gene (Pippucci et al. 2011. PubMed ID: 21211618; Noris et al. 2011. PubMed ID: 21467542; Daama et al. 2013. PubMed ID: 23869080; Marquez et al. 2014. PubMed ID: 24628296). Pathogenic variants in ANKRD26 accounted for 15% of inherited thrombocytopenia cases in one study of Japanese individuals (Kunishima et al. 2013. PubMed ID: 23434115). To date, almost all reported pathogenic variants in the ANKRD26 gene are found in the 5' UTR (Pippucci et al. 2011. PubMed ID: 21211618; Noris et al. 2011. PubMed ID: 21467542; Daama et al. 2013. PubMed ID: 23869080; Marquez et al. 2014. PubMed ID: 24628296). A duplication of one nucleotide in exon 33 that results in premature protein termination was reported in a patient with bone marrow failure syndrome (Ghemlas et al. 2015. PubMed ID: 26136524) and one nonsense variant was reported in exon 11 in a patient with epidermodysplasia verruciformis (Uddin et al. 2018. PubMed ID: 30147876). Pathogenic variants in ANKRD26 are inherited with nearly complete penetrance for the bleeding phenotype, but with incomplete penetrance for MDS/AML.
ANKRD26 is expressed in megakaryocytes and erythroid cells (Macaulay et al. 2007. PubMed ID: 17192395). The function of ANKRD26 is unknown, but data suggest it plays a role in megakaryocyte maturation (Noris et al. 2011. PubMed ID: 21467542).
Clinical Sensitivity - Sequencing with CNV PG-Select
Over 30 genes are known to be associated with inherited thrombocytopenias. Pathogenic variants in known genes are found in only about 50% of cases (Kunishima and Saito. 2006. PubMed ID: 16169642; Noris and Pecci. 2017. PubMed ID: 29222283). Pathogenic variants in ANKRD26 accounted for 15% of inherited thrombocytopenia cases in a study of Japanese individuals (Kunishima et al. 2013. PubMed ID: 23434115).
Testing Strategy
Copy number variants (CNVs) are also detected from NGS data. We utilize a CNV-calling algorithm that compares mean read depth and distribution for each target in the test sample against multiple matched controls. Neighboring target read depth and distribution and zygosity of any variants within each target region are used to reinforce CNV calls. All CNVs are confirmed using another technology such as aCGH, MLPA, or PCR before they are reported.
This test provides full coverage of all coding exons of the ANKRD26 gene plus coverage of 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.
Specifically, for the ANKRD26 gene, we provide coverage of the 5' UTR where pathogenic variants in ANKRD26 are primarily located.
Indications for Test
Patients with abnormal platelet function, or low platelet counts, and patients with a personal or family history of MDS/AML .
Patients with abnormal platelet function, or low platelet counts, and patients with a personal or family history of MDS/AML .
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| ANKRD26 | 610855 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Thrombocytopenia 2 | AD | 188000 |
Related Tests
| Name |
|---|
| Bleeding Disorders Panel |
| Hereditary Myelodysplastic Syndrome (MDS) / Acute Myeloid Leukemia (AML) Panel |
| Thrombocytopenia Panel |
Citations
- Balduini et al. 2013. PubMed ID: 23397552
- Churpek et al. 2013. PubMed ID: 22691122
- Daama et al. 2013. PubMed ID: 23869080
- Drachman et al. 2000. PubMed ID: 10891439
- Furutani and Shimamura. 2017. PubMed ID: 28297620
- Gandhi et al. 2003. PubMed ID: 12890928
- Ghemlas et al. 2015. PubMed ID: 26136524
- Kunishima and Saito. 2006. PubMed ID: 16169642
- Kunishima et al. 2013. PubMed ID: 23434115
- Macaulay et al. 2007. PubMed ID: 17192395
- Marquez et al. 2014. PubMed ID: 24628296
- Noris and Pecci. 2017. PubMed ID: 29222283
- Noris et al. 2011. PubMed ID: 21467542
- Noris et al. 2013. PubMed ID: 24030261
- Pippucci et al. 2011. PubMed ID: 21211618
- Punzo et al. 2010. PubMed ID: 20626622
- Savoia et al. 1999. PubMed ID: 10521306
- Uddin et al. 2018. PubMed ID: 30147876
Ordering/Specimens
Ordering Options
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
myPrevent - Online Ordering
- The test can be added to your online orders in the Summary and Pricing section.
- Once the test has been added log in to myPrevent to fill out an online requisition form.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
Requisition Form
- A completed requisition form must accompany all specimens.
- Billing information along with specimen and shipping instructions are within the requisition form.
- All testing must be ordered by a qualified healthcare provider.
For Requisition Forms, visit our Forms page
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
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