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Cleidocranial Dysplasia (CCD) via the RUNX2 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
RUNX2 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8267RUNX281479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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 platform).

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

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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.


Genetic Counselors


  • Juan Dong, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Cleidocranial dysplasia (OMIM#119600) is a skeletal disorder characterized by delayed closure of the cranial sutures, hypoplastic or absent clavicles, increased head circumference, multiple dental abnormalities, and short stature (Otto et al. Hum Mutat 19:209–216, 2002). Hand abnormalities such as brachydactyly, tapering fingers, and short, broad thumbs are also common. Manifestations vary among individuals in the same family.


Cleidocranial dysplasia is inherited in an autosomal dominant manner with high penetrance and extreme variability (Zhou et al. Hum Mol Genet 8:2311–2316, 1999). The proportion of cases caused by a de novo variant is high. RUNX2 (known previously as CBFA1) is the only gene known to be associated with CCD. RUNX2 encodes runt-related transcription factor 2, which is involved in osteoblast differentiation and skeletal morphogenesis. RUNX2 is essential for osteoblast differentiation during intramembranous as well as chondrocyte maturation during endochondral ossification (Zheng et al. Am J Hum Genet 77:305–312, 2005). This protein contains an N-terminal stretch of consecutive polyglutamine and polyalanine repeats, known as the Q/A domain or the runt domain, and a C-terminal proline/serine/threonine-rich (PST) activation domain. The runt domain is a 128-amino-acid polypeptide motif that has the unique ability to independently mediate DNA binding and protein heterodimerization (Zhou et al. 1999). Most variants in RUNX2 are missense, nonsense, frameshift, and splice site variants. The majority of RUNX2 variants in individuals with classic CCD affect the runt domain, and most variants are predicted to abolish DNA binding (Lee et al. Nat Genet 16:307–310, 1997; Otto et al. 2002).

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect disease variants in 60-70% of individuals with a clinical diagnosis of CCD (Otto et al. 2002; Ott et al. Hum Mutat 31:1587-1593, 2010). Heterozygous deletions of all or part of the RUNX2 gene, which would not be detected by sequencing, may be present in ~10% of all patients with CCD (Ott et al. 2010).

Testing Strategy

This test provides full coverage of all coding exons of the RUNX2 gene plus 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

Candidates for this test are patients with clinical and radiographic findings consistent with CCD and family members of patients who have a known RUNX2 variant.


Official Gene Symbol OMIM ID
RUNX2 600211
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Cleidocranial Dysostosis AD 119600


  • Lee, B., et.al. (1997). "Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia." Nat Genet 16(3): 307-10. PubMed ID: 9207800
  • Ott, C. E., et.al. (2010). "Deletions of the RUNX2 gene are present in about 10% of individuals with cleidocranial dysplasia." Hum Mutat 31(8): E1587-93. PubMed ID: 20648631
  • Otto, F., et.al. (2002). "Mutations in the RUNX2 gene in patients with cleidocranial dysplasia." Hum Mutat 19(3): 209-16. PubMed ID: 11857736
  • Zheng, Q., et.al. (2005). "Dysregulation of chondrogenesis in human cleidocranial dysplasia." Am J Hum Genet 77(2): 305-12. PubMed ID: 15952089
  • Zhou, G., et.al. (1999). "CBFA1 mutation analysis and functional correlation with phenotypic variability in cleidocranial dysplasia." Hum Mol Genet 8(12): 2311-6. PubMed ID: 10545612


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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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View Ordering Instructions

1) Select Test Method (Platform)

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2) Select Additional Test Options

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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