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Thrombocytopenia and Bleeding Disorder, Platelet Type 19 via the PRKACG Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
12611 PRKACG 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
12611PRKACG81479 81479,81479 $890 Order Options and Pricing

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

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.

Pathogenic variants in PRKACG are associated with a rare form of inherited thrombocytopenia defined as bleeding disorder, platelet-type, 19 (BDPLT19) that has been reported in only one family to date (Manchev et al. 2014. PubMed ID:25061177). PRKACG-related thrombocytopenia is characterized by severe thrombocytopenia (5-8/µL), large platelets, moderate bleeding, epistaxis, and cutaneous hematomas (Manchev et al. 2014. PubMed ID:25061177).

Genetics

Inheritance is autosomal recessive and to date, only one pathogenic variant in PRKACG has been reported to be causative for thrombocytopenia. A homozygous missense variant, c.222C>G (p.Ile74Met), was reported in one family with a history of early childhood onset, severe macrothrombocytopenia, and bleeding diatheses (Manchev et al. 2014. PubMed ID: 25061177).

The PRKACG gene encodes the γ-catalytic subunit of the cyclic adenosine monophosphate-dependent protein kinase. Data suggest that the PRKACG protein plays a role in proplatelet formation and that pathogenic variants have a negative effect on the platelet cytoskeletal protein filamin A (Manchev et al. 2014. PubMed ID: 25061177).

Clinical Sensitivity - Sequencing with CNV PGxome

Over 30 genes are known to be associated with inherited thrombocytopenias (IT). 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). PRKACG-related IT is a rare form of IT which has been reported in only one family to date.

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 PRKACG 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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Patients with a personal or family history of low platelet counts and mild to moderate bleeding diatheses. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PRKACG.

Gene

Official Gene Symbol OMIM ID
PRKACG 176893
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Bleeding Disorder, Platelet-Type, 19 AR 616176

Related Test

Name
Bleeding Disorders Panel

Citations

  • Balduini et al. 2013. PubMed ID: 23397552
  • Churpek et al. 2013. PubMed ID: 22691122
  • Furutani and Shimamura. 2017. PubMed ID: 28297620
  • Kunishima and Saito. 2006. PubMed ID: 16169642
  • Manchev et al. 2014. PubMed ID: 25061177
  • Noris and Pecci. 2017. PubMed ID: 29222283

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


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.
Total Price: $
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