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Thrombocytopenia 5 and Predisposition for Hematologic Malignancy via the ETV6 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7097 ETV6 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7097ETV681479 81479,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 13 days 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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Siwu Peng, PhD

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.

Variants in ETV6 have been identified in several families with autosomal dominant thrombocytopenia (Thrombocytopenia 5) and who have mild-to-moderate bleeding tendencies and an increased risk of bone marrow failure and development of hematologic malignancies including primarily acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) (Bluteau et al. 2018. PubMed ID: 29146883; Zhang et al. 2015. PubMed ID: 25581430; Topka et al. 2015. PubMed ID: 26102509; Noetzli et al. 2015. PubMed ID: 25807284). ETV6-related thrombocytopenia accounts for about 5% of inherited thrombocytopenias, and approximately 25% of patients with ETV6-related thrombocytopenia acquire ALL and other hematologic malignancies (Noris and Pecci. 2017. PubMed ID: 29222283). In one study, ETV6 deficient platelets were shown to have a rounder shape, variable size, and decreased function compared to normal platelets (Poggi et al. 2017. PubMed ID: 27663637).

Genetics

Somatic variants in ETV6 including gene fusions, deletions, and single nucleotide substitutions are frequently found in hematopoietic malignancies (Wang et al. 2014. PubMed ID: 24997145), but only recently have germline missense, nonsense, and other variants been found to segregate with hematopoietic malignancies (Zhang et al. 2015. PubMed ID: 25581430; Moriyama et al. 2015. PubMed ID: 26522332). ETV6 variants segregate completely with thrombocytopenia in affected families, but penetrance for malignancies is incomplete (Zhang et al. 2015. PubMed ID: 25581430; Topka et al. 2015. PubMed ID: 26102509; Noetzli et al. 2015. PubMed ID: 25807284). Functional studies of pathogenic ETV6 variants found in different kindreds show decreased DNA-binding and / or mislocalization of ETV6 protein suggesting that abnormal ETV6 functions in a dominant-negative manner that impairs hematopoiesis (Topka et al. 2015; Zhang et al. 2015).

ETV6 encodes a transcription repressor important for blood cell development and differentiation, in particular, platelet formation (Wang et al. 1998. PubMed ID: 9694803; Poggi et al. 2017. PubMed ID: 27663637).

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). ETV6-related thrombocytopenia accounts for about 5% of inherited thrombocytopenias, and approximately 25% of patients with ETV6-related thrombocytopenia acquire ALL and other hematologic malignancies (Noris and Pecci. 2017. PubMed ID: 29222283).

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 ETV6 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.

Indications for Test

Patients with a personal or family history of functional and morphological platelet defects, low platelet counts, and hematologic malignancy.

Gene

Official Gene Symbol OMIM ID
ETV6 600618
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Thrombocytopenia 5 AD 616216

Related Tests

Name
Bleeding Disorders Panel
Hereditary Myelodysplastic Syndrome (MDS) / Acute Myeloid Leukemia (AML) Panel
Pediatric Cancer Panel
Thrombocytopenia Panel

Citations

  • Balduini et al. 2013. PubMed ID: 23397552
  • Bluteau et al. 2018. PubMed ID: 29146883
  • Churpek et al. 2013. PubMed ID: 22691122
  • Furutani and Shimamura. 2017. PubMed ID: 28297620
  • Kunishima and Saito. 2006. PubMed ID: 16169642
  • Moriyama et al. 2015. PubMed ID: 26522332
  • Noetzli et al. 2015. PubMed ID: 25807284
  • Noris and Pecci. 2017. PubMed ID: 29222283
  • Poggi et al. 2017. PubMed ID: 27663637
  • Topka et al. 2015. PubMed ID: 26102509
  • Wang et al. 1998. PubMed ID: 9694803
  • Wang et al. 2014. PubMed ID: 24997145
  • Zhang et al. 2015. PubMed ID: 25581430

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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