Cleft Lip with or without Cleft Palate via the ARHGAP29 Gene
Summary and Pricing
Test Method
Exome Sequencing with CNV DetectionTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
12641 | ARHGAP29 | 81479 | 81479,81479 | $990 | 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 platform).
Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).
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
Pathogenic variants in the ARHGAP29 gene are associated with non-syndromic (isolated) cleft lip with or without cleft palate (CL/P). CL/P is the most common type of congenital craniofacial anomaly identified in newborns, occurring at a rate of 1-2 per 1,000 live births (IPDTOC Working Group. 2011. PubMed ID: 20507242; Mai et al. 2014. PubMed ID: 25399767; Dixon et al. 2011. PubMed ID: 21331089). CL/P may be identified on prenatal ultrasound or at birth. Individuals with non-syndromic CL/P may have difficulties feeding, speaking, and hearing, and may require surgery, dental treatment, speech therapy, audiology, and psychological counseling (Burg et al. 2016. PubMed ID: 26973535). Genetic testing may aide in establishing diagnosis and prognosis, and may assist in reproductive planning.
Genetics
ARHGAP29-associated CL/P is inherited in an autosomal dominant manner and displays incomplete penetrance and variable expressivity (Leslie et al. 2012. PubMed ID: 23008150; Liu et al. 2017. PubMed ID: 28029220; Savastano et al. 2017. PubMed ID: 27350171). Whilst no de novo pathogenic variants have been reported in the ARHGAP29 gene to date, pathogenic variants have been reported to arise de novo in other genes associated with orofacial clefting (Peyrard-Janvid et al. 2005. PubMed ID: 16160700; Peyrard-Janvid et al. 2014. PubMed ID: 24360809). Pathogenic missense and loss of function variants have been reported (Leslie et al. 2012. PubMed ID: 23008150; Butali et al. 2014. PubMed ID: 25081408; Chandrasekharan and Ramanathan. 2014. PubMed ID: 25512736; Letra et al. 2014. PubMed ID: 25163644; Leslie et al. 2015. PubMed ID: 25704602; Gowans et al. 2016. PubMed ID: 27369588; Liu et al. 2017. PubMed ID: 28029220). To date, no pathogenic copy number variants (CNVs) or large chromosomal rearrangements have been associated with ARHGAP29-related CL/P. Estimates from gene constraint models suggest this gene is intolerant of loss of function variation, but relatively tolerant of missense variation (https://gnomad.broadinstitute.org/gene/ENSG00000137962). However caution should be used when considering these metrics due to the variable penetrance and expressivity of ARHGAP29-related CL/P.
ARHGAP29 encodes a GTPase-activating protein, which is involved in the regulation of small GTP binding proteins that affect actin re-arrangement, cell-cell and cell-matrix adhesion, and cell spreading, all of which are critical for craniofacial development (Saras et al. 1997. PubMed ID: 9305890; Myagmar et al. 2005. PubMed ID: 15752761; Post et al. 2013. PubMed ID: 23798437; Post et al. 2015. PubMed ID: 25963656). Expression has been detected in several tissues, including the palatal shelves and oral epithelium during craniofacial development in mouse embryos (Saras et al. 1997. PubMed ID: 9305890; Leslie et al. 2012. PubMed ID: 23008150; Paul et al. 2017. PubMed ID: 28817352).
ARHGAP29 is one of many genes associated with CL/P (Kousa et al. 2017. PubMed ID: 27933721). Please refer to our Cleft Lip/Cleft Palate Panel for additional genes associated with orofacial clefting.
Clinical Sensitivity - Sequencing with CNV PGxome
Pathogenic variants in the ARHGAP29 gene are emerging as a rare cause of non-syndromic CL/P, having been reported in cases-control studies, and a limited number of isolated cases and multigenerational families (Leslie et al. 2012. PubMed ID: 23008150; Butali et al. 2014. PubMed ID: 25081408; Chandrasekharan and Ramanathan. 2014. PubMed ID: 25512736; Letra et al. 2014. PubMed ID: 25163644; Leslie et al. 2015. PubMed ID: 25704602; Gowans et al. 2016. PubMed ID: 27369588; Liu et al. 2017. PubMed ID: 28029220). Clinical sensitivity is difficult to estimate for ARHGAP29. In one study, rare ARHGAP29 variants were detected in 7 of 1,440 cases with non-syndromic CL/P (0.5%) and absent in controls (Leslie et al. 2012. PubMed ID: 23008150).
Testing Strategy
This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.
This test provides full coverage of all coding exons of the ARHGAP29 genes 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 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 features consistent with a diagnosis of non-syndromic CL/P. We will also sequence any single exon (Test #100) in family members of patients with a known pathogenic variant or to confirm research results.
Candidates for this test are patients with clinical features consistent with a diagnosis of non-syndromic CL/P. We will also sequence any single exon (Test #100) in family members of patients with a known pathogenic variant or to confirm research results.
Gene
Official Gene Symbol | OMIM ID |
---|---|
ARHGAP29 | 610496 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Disease
Name | Inheritance | OMIM ID |
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Related Test
Name |
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Cleft Lip/Cleft Palate Panel |
Citations
- Burg et al. 2016. PubMed ID: 26973535
- Butali et al. 2014. PubMed ID: 25081408
- Chandrasekharan and Ramanathan. 2014. PubMed ID: 25512736
- Dixon et al. 2011. PubMed ID: 21331089
- Gowans et al. 2016. PubMed ID: 27369588
- IPDTOC Working Group. 2011. PubMed ID: 20507242
- Kousa et al. 2017. PubMed ID: 27933721
- Leslie et al. 2012. PubMed ID: 23008150
- Leslie et al. 2015. PubMed ID: 25704602
- Letra et al. 2014. PubMed ID: 25163644
- Liu et al. 2017. PubMed ID: 28029220
- Mai et al. 2014. PubMed ID: 25399767
- Myagmar et al. 2005. PubMed ID: 15752761
- Paul et al. 2017. PubMed ID: 28817352
- Peyrard-Janvid et al. 2005. PubMed ID: 16160700
- Peyrard-Janvid et al. 2014. PubMed ID: 24360809
- Post et al. 2013. PubMed ID: 23798437
- Post et al. 2015. PubMed ID: 25963656
- Saras et al. 1997. PubMed ID: 9305890
- Savastano et al. 2017. PubMed ID: 27350171
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
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.