- Is a 100 gene panel that includes assessment of non-coding variants
Is ideal for patients with a clinical suspicion of Bardet-Biedl syndrome, Joubert syndrome, Meckel syndrome, nephronophthisis with or without retinal dystrophy, or complex ciliopathy phenotype.
Isn’t ideal for a patient with primary ciliary dyskinesia or isomerism/heterotaxy. For patients with a suspicion of primary ciliary dyskinesia, Primary Ciliary Dyskinesia Panel is recommended. For patients with isomerism/heterotaxy, Heterotaxy and Situs Inversus Panel is recommended.
Number of genes100
CPT codesSEQ 81404
The Blueprint Genetics Ciliopathy Panel (test code KI0701):
- Is a 100 gene panel that includes assessment of selected non-coding disease-causing variants
- Is available as PLUS analysis (sequencing analysis and deletion/duplication analysis), sequencing analysis only or deletion/duplication analysis only
Commonly used ICD-10 code(s) when ordering the Ciliopathy Panel
|Q61.9||Cystic kidney disease|
|Q61.5||Nephronophthisis with retinal dystrophy|
- EDTA blood, min. 1 ml
- Purified DNA, min. 3μg
- Saliva (Oragene DNA OG-500 kit)
Label the sample tube with your patient’s name, date of birth and the date of sample collection.
Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.
Ciliopathies are a group of disorders resulting from either abnormal formation or function of cilia. Mutations in ciliary gene are known to cause single organ phenotypes, as well as complex syndromes. Ciliopathies have a broad range of phenotypes encompassing a number of different autosomal recessive, dominant and X-linked syndromes. As cilia are a component of almost all cells, ciliary dysfunction can manifest as a collection of features that include retinal degeneration, renal disease and brain malformations. Additional features may include congenital fibrocystic diseases of the liver and pancreas, diabetes, obesity and skeletal dysplasias. Ciliopathies can result from a mutation at a single locus in one patient while mutations affecting a number of different loci can, at the same time, can result in a similar phenotype in other patients. Ciliopathies can be classified according to whether there is aberrant function in an intact cilium or complete absence/loss of the mature cilium. The latter is the case with severe multi-organ phenotypes.
Genes in the Ciliopathy Panel and their clinical significance
|ACVR2B||Heterotaxy, visceral, 4, autosomal||AD||1||2|
|ARL6||Bardet-Biedl syndrome, Retinitis pigmentosa||AR||13||21|
|ARMC9||Joubert syndrome 30||AR||11||10|
|BBIP1#||Bardet-Biedl syndrome 18||AR||1||1|
|BBS2||Bardet-Biedl syndrome, Retinitis pigmentosa||AR||32||90|
|C2CD3||Orofaciodigital syndrome XIV||AR||9||9|
|C5ORF42||Orofaciodigital syndrome, Joubert syndrome||AR||68||98|
|C8ORF37||Retinitis pigmentosa, Cone rod dystrophy||AR||8||15|
|C21ORF2||Retinal dystrophy with or without macular staphyloma (RDMS), Spondylometaphyseal dysplasia, axial (SMDAX)||AR||12||19|
|CC2D2A||COACH syndrome, Joubert syndrome, Meckel syndrome||AR||71||86|
|CENPF||Ciliary dyskinesia -Lethal Ciliopathy||AR||11||7|
|CEP120||Short-rib thoracic dysplasia 13 with or without polydactyly||AR||3||9|
|CEP290*||Bardet-Biedl syndrome, Leber congenital amaurosis, Joubert syndrome, Senior-Loken syndrome, Meckel syndrome||AR||96||266|
|CRB2||Focal segmental glomerulosclerosis, Ventriculomegaly with cystic kidney disease||AR||11||21|
|CSPP1||Jeune asphyxiating thoracic dystrophy, Joubert syndrome||AR||25||25|
|DDX59||Orofaciodigital syndrome V||AR||2||4|
|DYNC2H1||Short -rib thoracic dysplasia with or without polydactyly type 1, Short -rib thoracic dysplasia with or without polydactyly type 3, Asphyxiating thoracic dysplasia (ATD; Jeune), SRPS type 2 (Majewski)||AR/Digenic||46||101|
|DYNC2LI1||Short-rib throacic dysplasia 15 with polydactyly||14||8|
|EVC||Weyers acrofacial dysostosis, Ellis-van Creveld syndrome||AD/AR||11||80|
|EVC2||Ellis-van Creveld syndrome, Weyers acrodental dysostosis||AD/AR||26||67|
|FAM58A||Toe syndactyly, telecanthus, and anogenital and renal malformations (STAR syndrome)||XL||6||9|
|GLI3||Acrocallosal syndrome, Pallister-Hall syndrome, Grieg cephalopolysndactyly syndrome, Postaxial polydactyly type A, Preaxial polydactyly type 3, Preaxial polydactyly type 4||AD||56||222|
|IFT43||Cranioectodermal dysplasia 3||AR||1||5|
|IFT80||Short -rib thoracic dysplasia with or without polydactyly, Asphyxiating thoracic dysplasia (ATD; Jeune)||AR||8||7|
|IFT81||Short rib thoracic dysplasia with polydactyly, Cone-Rod dystrophy, autosomal recessive||AR||8|
|IFT122*||Sensenbrenner syndrome, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 1, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 2||AR||11||17|
|IFT140||Short -rib thoracic dysplasia with or without polydactyly, Asphyxiating thoracic dysplasia (ATD; Jeune)||AR||19||52|
|IFT172||Retinitis pigmentosa, Short -rib thoracic dysplasia with or without polydactyly, Asphyxiating thoracic dysplasia (ATD; Jeune)||AR||20||23|
|INPP5E||Joubert syndrome, Mental retardation, truncal obesity, retinal dystrophy, and micropenis (MORM syndrome)||AR||23||44|
|KIAA0556||Joubert syndrome 26||AR||1||2|
|KIAA0586||Short rib thoracic dysplasia with polydactyly, Joubert syndrome||AR||20||29|
|KIAA0753||Orofaciodigital syndrome XV||AR||3||4|
|KIF7||Acrocallosal syndrome, Hydrolethalus syndrome, Al-Gazali-Bakalinova syndrome, Joubert syndrome||AR/Digenic||15||40|
|KIF14||Meckel syndrome 12||AR||2||6|
|LEFTY2*||Left-right axis malformations||AD||3||3|
|LZTFL1||Bardet-Biedl syndrome 17||AR||5||3|
|MKKS||Bardet-Biedl syndrome, McKusick-Kaufman syndrome||AR||15||59|
|MKS1||Bardet-Biedl syndrome, Meckel syndrome||AR||42||51|
|NEK1||Short -rib thoracic dysplasia with or without polydactyly, SRPS type 2 (Majewski)||AR/Digenic||10||16|
|NPHP1||Nephronophthisis, Joubert syndrome, Senior-Loken syndrome||AR||14||73|
|NPHP3||Nephronophthisis, Renal-hepatic-pancreatic dysplasia, Meckel syndrome||AR||24||72|
|NPHP4||Nephronophthisis, Senior-Loken syndrome||AR||12||108|
|OFD1||Simpson-Golabi-Behmel syndrome, Retinitis pigmentosa, Orofaciodigital syndrome, Joubert syndrome||XL||133||156|
|PDE6D||Joubert syndrome 22||AR||3||1|
|PKD1*||Polycystic kidney disease||AD||104||1655|
|PKD2||Polycystic kidney disease||AD||28||287|
|PKHD1||Polycystic kidney disease||AR||154||520|
|PMM2||Congenital disorder of glycosylation||AR||58||123|
|PNPLA6||Laurence-Moon syndrome, Boucher-Neuhauser syndrome, Spastic paraplegia 39||AR||22||50|
|POC1B||Cone-rod dystrophy 20||AR||4||3|
|RPGRIP1L||COACH syndrome, Joubert syndrome, Meckel syndrome, Retinal degeneration in ciliopathy, modifier||AD/AR||35||45|
|SDCCAG8||Bardet-Biedl syndrome, Senior-Loken syndrome||AR||12||18|
|TCTN2||Joubert syndrome, Meckel syndrome||AR||17||13|
|TCTN3||Orofaciodigital syndrome (Mohr-Majewski syndrome), Joubert syndrome||AR||9||10|
|TMEM67||Nephronophthisis, COACH syndrome, Joubert syndrome, Meckel syndrome||AR||82||153|
|TMEM216||Joubert syndrome, Meckel syndrome||AR||14||8|
|TMEM231||Joubert syndrome, Meckel syndrome||AR||9||19|
|TRAF3IP1||Senior-Loken syndrome 9||AR||6||10|
|TRIM32||Bardet-Biedl syndrome, Muscular dystrophy, limb-girdle||AR||11||16|
|TTC8||Bardet-Biedl syndrome, Retinitis pigmentosa||AR||5||16|
|TTC21B||Short-rib thoracic dysplasia, Nephronophthisis, Asphyxiating thoracic dysplasia (ATD; Jeune)||AR||8||53|
|USP9X||Mental retardation, X-linked 99, Mental retardation, X-linked 99, syndromic, female restricted||XL||21||25|
|WDPCP||Meckel-Gruber syndrome, modifier, Bardet-Biedl syndrome, Congenital heart defects, hamartomas of tongue, and polysyndactyly||AR||6||7|
|WDR19||Retinitis pigmentosa, Nephronophthisis, Short -rib thoracic dysplasia with or without polydactyly, Senior-Loken syndrome, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 1, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 2, Asphyxiating thoracic dysplasia (ATD; Jeune)||AD/AR||20||28|
|WDR34||Short -rib thoracic dysplasia with or without polydactyly, Asphyxiating thoracic dysplasia (ATD; Jeune)||AR||10||15|
|WDR35||Cranioectodermal dysplasia (Levin-Sensenbrenner) type 1, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 2, Short rib-polydactyly syndrome type 5||AR||19||28|
|WDR60||Short-rib thoracic dysplasia 8 with or without polydactyly||AR||5||5|
|ZIC3||Heterotaxy, visceral, VACTERL association, Congenital heart defects, nonsyndromic||XL||13||41|
|ZNF423||Nephronophthisis, Joubert syndrome||AD/AR||10||7|
* Some, or all, of the gene is duplicated in the genome. Read more.
# The gene has suboptimal coverage (means <90% of the gene’s target nucleotides are covered at >20x with mapping quality score (MQ>20) reads).
The sensitivity to detect variants may be limited in genes marked with an asterisk (*) or number sign (#)
Gene refers to the HGNC approved gene symbol; Inheritance refers to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR), X-linked (XL), X-linked dominant (XLD) and X-linked recessive (XLR); ClinVar refers to the number of variants in the gene classified as pathogenic or likely pathogenic in this database (ClinVar); HGMD refers to the number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD). The list of associated, gene specific phenotypes are generated from CGD or Orphanet databases.
Non-coding variants covered by the panel
|Gene||Genomic location HG19||HGVS||RefSeq||RS-number|
Added and removed genes from the panel
|Genes added||Genes removed|
|ACVR2B ARMC9 BBIP1 C21ORF2 C2CD3 C8ORF37 CEP104 CEP120 CRB2 DDX59 DHCR7 DYNC2H1 DYNC2LI1 EVC EVC2 FAM58A GLI2 GLI3 HYLS1 IFT122 IFT140 IFT43 IFT80 IFT81 KIAA0556 KIAA0753 KIF14 LEFTY2 LZTFL1 MAPKBP1 NEK1 NODAL PDE6D PKD1 PKD2 PKHD1 PMM2 PNPLA6 POC1B TRAF3IP1 USP9X WDPCP WDR34 WDR35 WDR60 ZIC3||ARMC4 C21ORF59 CCDC103 CCDC114 CCDC39 CCDC40 CCDC65 CCNO CFTR DNAAF1 DNAAF2 DNAAF3 DNAAF5 DNAH11 DNAH5 DNAI1 DNAI2 DNAL1 DRC1 DYX1C1 HYDIN LRRC6 NME8 RPGR RSPH1 RSPH4A RSPH9 SPAG1 ZMYND10|
Test strengthThe strengths of this test include:
- CAP and ISO-15189 accreditations covering all operations at Blueprint Genetics including all Whole Exome Sequencing, NGS panels and confirmatory testing
- CLIA-certified personnel performing clinical testing in a CLIA-certified laboratory
- Powerful sequencing technologies, advanced target enrichment methods and precision bioinformatics pipelines ensure superior analytical performance
- Careful construction of clinically effective and scientifically justified gene panels
- Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level
- Our publically available analytic validation demonstrating complete details of test performance
- 1479 non-coding disease causing variants in Blueprint WES assay (please see below ‘Non-coding disease causing variants covered by this panel’)
- Our rigorous variant classification based on modified ACMG variant classification scheme
- Our systematic clinical interpretation workflow using proprietary software enabling accurate and traceable processing of NGS data
- Our comprehensive clinical statements
Genes with suboptimal coverage in our assay are marked with number sign (#) and genes with partial, or whole gene, segmental duplications in the human genome are marked with an asterisk (*) if they overlap with the UCSC pseudogene regions. Gene is considered to have suboptimal coverage when >90% of the gene's target nucleotides are not covered at >20x with mapping quality score (MQ>20) reads. The technology may have limited sensitivity to detect variants in genes marked with these symbols (please see the Panel content table above).This test does not detect the following:
- Complex inversions
- Gene conversions
- Balanced translocations
- Mitochondrial DNA variants
- Repeat expansion disorders unless specifically mentioned
- Non-coding variants deeper than ±20 base pairs from exon-intron boundary unless otherwise indicated (please see above Panel Content / non-coding variants covered by the panel).
This test may not reliably detect the following:
- Low level mosaicism
- Stretches of mononucleotide repeats
- Indels larger than 50bp
- Single exon deletions or duplications
- Variants within pseudogene regions/duplicated segments
The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.
For additional information, please refer to the Test performance section and see our Analytic Validation.
The Blueprint Genetics ciliopathy panel covers classical genes associated with Bardet-Biedl syndrome, Joubert syndrome, Meckel syndrome, cystic kidney disease and nephronophthisis with retinal dystrophy. The genes on the panel have been carefully selected based on scientific literature, mutation databases and our experience.
Our panels are sliced from our high-quality whole exome sequencing data. Please see our sequencing and detection performance table for different types of alterations at the whole exome level (Table).
Assays have been validated for different starting materials including EDTA-blood, isolated DNA (no FFPE), saliva and dry blood spots (filter card) and all provide high-quality results. The diagnostic yield varies substantially depending on the assay used, referring healthcare professional, hospital and country. Blueprint Genetics' Plus Analysis (Seq+Del/Dup) maximizes the chance to find a molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be a cost-effective first line test if your patient's phenotype is suggestive of a specific mutation type.
Performance of Blueprint Genetics Whole Exome Sequencing (WES) assay. All individual panels are sliced from WES data.
|Sensitivity % (TP/(TP+FN)||Specificity %|
|Single nucleotide variants||99.65% (412,456/413,893)||>99.99%|
|Insertions, deletions and indels by sequence analysis|
|1-10 bps||96.94% (17,070/17,608)||>99.99%|
|11-50 bps||99.07% (957/966)||>99.99%|
|Copy number variants (exon level dels/dups)|
|Clinical samples (small CNVs, n=52)|
|1 exon level deletion||92.3% (24/26)||NA|
|2 exons level deletion/duplication||100.0% (11/11)||NA|
|3-7 exons level deletion/duplication||93.3% (14/15)||NA|
|Microdeletion/-duplication sdrs (large CNVs, n=37))|
|Size range (0.1-47 Mb)||100% (37/37)|
|Simulated CNV detection|
|2 exons level deletion/duplication||90.98% (7,357/8,086)||99.96%|
|5 exons level deletion/duplication||98.63% (7,975/8,086)||99.98%|
|The performance presented above reached by WES with the following coverage metrics|
|Mean sequencing depth at exome level||174x|
|Nucleotides with >20x sequencing coverage (%)||99.4%|
The target region for each gene includes coding exons and ±20 base pairs from the exon-intron boundary. In addition, the panel includes non-coding variants if listed above (Non-coding variants covered by the panel). Some regions of the gene(s) may be removed from the panel if specifically mentioned in the ‘Test limitations” section above. The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. Our pipeline is streamlined to maximize sensitivity without sacrificing specificity. We have incorporated a number of reference population databases and mutation databases such as, but not limited, to 1000 Genomes Project, gnomAD, ClinVar and HGMD into our clinical interpretation software to make the process effective and efficient. For missense variants, in silico variant prediction tools such as SIFT, PolyPhen, MutationTaster are used to assist with variant classification. Through our online ordering and statement reporting system, Nucleus, the customer has an access to details of the analysis, including patient specific sequencing metrics, a gene level coverage plot and a list of regions with inadequate coverage if present. This reflects our mission to build fully transparent diagnostics where customers have easy access to crucial details of the analysis process.
We provide customers with the most comprehensive clinical report available on the market. Clinical interpretation requires a fundamental understanding of clinical genetics and genetic principles. At Blueprint Genetics, our PhD molecular geneticists, medical geneticists and clinical consultants prepare the clinical statement together by evaluating the identified variants in the context of the phenotypic information provided in the requisition form. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals regardless of whether they have formal training in genetics.
Variant classification is the corner stone of clinical interpretation and resulting patient management decisions. Our classifications follow the Blueprint Genetics Variant Classification Schemes based on the ACMG guideline 2015. Minor modifications were made to increase reproducibility of the variant classification and improve the clinical validity of the report. Our experience with tens of thousands of clinical cases analyzed at our laboratory allowed us to further develop the industry standard.
The final step in the analysis of sequence variants is confirmation of variants classified as pathogenic or likely pathogenic using bi-directional Sanger sequencing. Variant(s) fulfilling all of the following criteria are not Sanger confirmed: 1) the variant quality score is above the internal threshold for a true positive call, 2) an unambiguous IGV in-line with the variant call and 3) previous Sanger confirmation of the same variant at least three times at Blueprint Genetics. Reported variants of uncertain significance are confirmed with bi-directional Sanger sequencing only if the quality score is below our internally defined quality score for true positive call. Reported copy number variations with a size <10 exons are confirmed by orthogonal methods such as qPCR if the specific CNV has been seen less than three times at Blueprint Genetics.
Our clinical statement includes tables for sequencing and copy number variants that include basic variant information (genomic coordinates, HGVS nomenclature, zygosity, allele frequencies, in silico predictions, OMIM phenotypes and classification of the variant). In addition, the statement includes detailed descriptions of the variant, gene and phenotype(s) including the role of the specific gene in human disease, the mutation profile, information about the gene’s variation in population cohorts and detailed information about related phenotypes. We also provide links to the references used, congress abstracts and mutation databases to help our customers further evaluate the reported findings if desired. The conclusion summarizes all of the existing information and provides our rationale for the classification of the variant.
Identification of pathogenic or likely pathogenic variants in dominant disorders or their combinations in different alleles in recessive disorders are considered molecular confirmation of the clinical diagnosis. In these cases, family member testing can be used for risk stratification within the family. In the case of variants of uncertain significance (VUS), we do not recommend family member risk stratification based on the VUS result. Furthermore, in the case of VUS, we do not recommend the use of genetic information in patient management or genetic counseling. For eligible cases, Blueprint Genetics offers a no charge service to investigate the role of reported VUS (VUS Clarification Service).
Our interpretation team analyzes millions of variants from thousands of individuals with rare diseases. Thus, our database, and our understanding of variants and related phenotypes, is growing by leaps and bounds. Our laboratory is therefore well positioned to re-classify previously reported variants as new information becomes available. If a variant previously reported by Blueprint Genetics is re-classified, our laboratory will issue a follow-up statement to the original ordering health care provider at no additional cost.