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Autosomal Dominant, Non-Syndromic Holoprosencephaly via the GAS1 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
GAS1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
10043GAS181479 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


  • Stela Berisha, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Holoprosencephaly (HPE, OMIM 236100) is the most common developmental anomaly of the human forebrain and midface affecting 1 in 16,000 live births (Solomon et al. GeneReviews, 2011) and approximately 1 in 200 spontaneous abortions (Orioli et al. Hum Genet 109:1-6, 2001). HPE results from failure of the developing forebrain to divide into two hemispheres and causes a continuum of structural brain malformations ranging from alobar HPE to semilobar HPE to lobar HPE. In addition to the structural brain abnormality, patients with HPE may exhibit variable craniofacial anomalies, including cyclopia, ocular hypotelorism, structurally and positionally abnormal proboscis, bilateral cleft lip, anophthalmia or microophthalmia, absent nasal septum, flat nose, or single central incisor. Because incomplete penetrance is a feature of dominantly inherited HPE, relatively normal facial appearance can be seen in individuals who have causative gene variants and affected first degree relatives. Developmental delay is a nearly constant clinical manifestation of HPE. Severely affected newborns with alobar HPE, cyclopia, and ethmocephaly usually do not live beyond the first week of life (Croen et al. Am J Med Genet 64:465-472, 1996), but survival is greater in those cases with less severe craniofacial anomalies (Barr and Cohen Am J Med Genet 89:116-120, 1999). Clinical signs present in patients with GAS1 variants range from classic HPE to HPE-like signs (Ribeiro et al. Am J Med Genet A. 152A:1688-1694, 2010; Pineda-Alvarez et al. Hum Genet, DOI 10.1007/s00439-011-1078-6, 2011).


Holoprosencephaly (HPE) has both genetic and non-genetic causes. Chromosome aneuploidy and structural abnormality are the overall most common cause accounting for 25%-50% of all cases; another 18%-25% of all cases occur as part of syndromes resulting from single gene variants (Solomon et al. GeneReviews, 2011). Nonsyndromic HPE is inherited as an autosomal dominant disorder with incomplete penetrance and intrafamilial variable expression. The GAS1 protein is a positive regulator of sonic hedgehog (SHH; Martinelli et al. Genes Dev 21:1231-1243, 2007), and it has been established that sequence variants in GAS1 impair its physical interaction with SHH (Pineda-Alvarez et al. 2011). Thus far, a small number of GAS1 variants have been reported, and all are amino acid substitutions (Ribeiro et al. Am J Med Genet A. 152A:1688-1694, 2010; Pineda-Alvarez et al. 2011). Most of the variants have been correlated with decreased GAS1-SHH binding affinity (Pineda-Alvarez et al. 2011).

Clinical Sensitivity - Sequencing with CNV PGxome

Among 394 unrelated patients referred for HPE spectrum clinical findings, Pineda-Alvarez et al. (2011) identified five novel variants in the GAS1 gene.

Testing Strategy

This test provides full coverage of all coding exons of the GAS1 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

Individuals with clinical findings consistent with holoprosencephaly.


Official Gene Symbol OMIM ID
GAS1 139185
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Holoprosencephaly Sequence 236100

Related Tests

Holoprosencephaly-2 (Autosomal Dominant, Nonsyndromic) via the SIX3 Gene
Holoprosencephaly-3 (Autosomal Dominant Nonsyndromic) via the SHH Gene
Holoprosencephaly-4 (Autosomal Dominant, Nonsyndromic) via the TGIF1 Gene
Holoprosencephaly-7 (Autosomal Dominant, Nonsyndromic) via the PTCH1 Gene


  • Barr, M., Jr., Cohen, M. M., Jr. (1999). "Holoprosencephaly survival and performance." Am J Med Genet 89(2): 116-20. PubMed ID: 10559767
  • Benjamin D Solomon (2011). "Holoprosencephaly Overview."
  • Benjamin D Solomon, et.al. (2011). "Holoprosencephaly Overview." PubMed ID: 20301702
  • Croen, L. A., et.al. (1996). "Holoprosencephaly: epidemiologic and clinical characteristics of a California population." Am J Med Genet 64(3): 465-72. PubMed ID: 8862623
  • Martinelli, D. C., Fan, C. M. (2007). "Gas1 extends the range of Hedgehog action by facilitating its signaling." Genes Dev 21(10): 1231-43. PubMed ID: 17504940
  • Orioli, I. M., et.al. (2001). "Identification of novel mutations in SHH and ZIC2 in a South American (ECLAMC) population with holoprosencephaly." Hum Genet 109(1): 1-6. PubMed ID: 11479728
  • Pineda-Alvarez, D. E., et.al. (2011). "Missense substitutions in the GAS1 protein present in holoprosencephaly patients reduce the affinity for its ligand, SHH." Hum Genet 131(2): 301-10. PubMed ID: 21842183
  • Ribeiro, L. A., et.al. (2010). "Holoprosencephaly and holoprosencephaly-like phenotype and GAS1 DNA sequence changes: Report of four Brazilian patients." Am J Med Genet A 152A(7): 1688-94. PubMed ID: 20583177


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