Achromatopsia (ACHM) via the ATF6 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 | |
---|---|---|---|---|---|
12627 | ATF6 | 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
Achromatopsia (ACHM) is a congenital, autosomal recessive retinal disorder characterized by total color blindness, decreased visual acuity (lower than 20/200), photophobia, nystagmus and absence of cone-mediated electroretinographic amplitudes at birth or early infancy (Kohl et al. 2005. PubMed ID: 15657609; Kohl et al. 2015. PubMed ID: 26029869; Pang et al. 2010. PubMed ID: 20238068). Estimated prevalence is 1/30,000 (Kohl et al. 2002. PubMed ID: 12077706).
With the advent of gene therapy and other types of treatments, the identification of causative genes and variants is becoming increasingly important.
Please see the links for clinical trials and management options below:
Genetics
ACHM is a heterogeneous disorder. To date, pathogenic variants in CNGA3, CNGB3, GNAT2, PDE6C, ATF6 and PDE6H have been reported to be causative for autosomal recessive ACHM (Ouechtati et al. 2011. PubMed ID: 21107338; Greenberg et al. 2014. PubMed ID: 24504161; Mastey et al. 2019. PubMed ID: 31237654). CNGA3 and CNGB3 are the major causative genes for ACHM (Kohl et al. 2005. PubMed ID: 15657609). A frameshift protein truncating variant in CNGB3 (c.1148del, p.Thr383Ilefs*13) has been reported as a predominant pathogenic variant (Kohl et al. 2005. PubMed ID: 15657609; Nishiguchi et al. 2005. PubMed ID: 15712225; Wiszniewski et al. 2007. PubMed ID: 17265047). This variant has been reported at a frequency of 0.2% in general population (http://gnomad.broadinstitute.org/variant/8-87656008-AG-A). To our knowledge, de novo variants have not been documented causative in the genes associated with ACHM (HGMD-Human Gene Mutation Database).
ATF6 encodes photoreceptor specific- activating transcription factor 6A, which is a key regulator of the unfolded protein response (UPR) and cellular endoplasmic reticulum (ER) homeostasis. These functions are essential for retina and photoreceptor survival (Kohl et al. 2015. PubMed ID: 26029869; Xu et al. 2015. PubMed ID: 26070061). Mice lacking ATF6 have been shown to have normal retinal morphology and function at a young age, but with increasing age they develop dysfunction of photoreceptor cells (Xu et al. 2015. PubMed ID: 26070061).
So far, about 15 causative ATF6 variants have been identified (missense/nonsense, splicing, small deletions and duplications that result in frameshift and protein truncation) (HGMD).
Clinical Sensitivity - Sequencing with CNV PGxome
Pathogenic variants in ATF6 are a rare cause of Achromatopsia. Kohl et al. reported that in their patient cohort, ~1% of European-ancestry individuals with Achromatopsia carried pathogenic variants in ATF6 (Kohl et al. 2015. PubMed ID: 26029869).
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 ATF6 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
All patients affected by Achromatopsia are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ATF6. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known pathogenic variants or to confirm research results.
All patients affected by Achromatopsia are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ATF6. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known pathogenic variants or to confirm research results.
Gene
Official Gene Symbol | OMIM ID |
---|---|
ATF6 | 605537 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Disease
Name | Inheritance | OMIM ID |
---|---|---|
Achromatopsia 7 | AR | 616517 |
Citations
- Greenberg et al. 2014. PubMed ID: 24504161
- Human Gene Mutation Database (Bio-base).
- Kohl et al. 2002. PubMed ID: 12077706
- Kohl et al. 2005. PubMed ID: 15657609
- Kohl et al. 2015. PubMed ID: 26029869
- Mastey et al. 2019. PubMed ID: 31237654
- Nishiguchi et al. 2005. PubMed ID: 15712225
- Ouechtati et al. 2011. PubMed ID: 21107338
- Pang et al. 2010. PubMed ID: 20238068
- Wiszniewski et al. 2007. PubMed ID: 17265047
- Xu et al. 2015. PubMed ID: 26070061
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.