- Is a 54 gene panel that includes assessment of non-coding variants
Is ideal for patients with a clinical suspicion / diagnosis of microphthalmia, anophthalmia or an anterior segment dysgenesis disorder.
Number of genes54
CPT codesSEQ 81479
The Blueprint Genetics Microphthalmia, Anophthalmia and Anterior Segment Dysgenesis Panel (test code OP0601):
Test Specific Strength
Assesses for non-coding disease-causing variants in one or more genes. For additional information, see the list of genes included in this panel.
Commonly used ICD-10 code(s) when ordering the Microphthalmia, Anophthalmia and Anterior Segment Dysgenesis Panel
|Q11.0||Isolated anophthalmia - microphthalmia|
- Blood (min. 1ml) in an EDTA tube
- Extracted DNA, min. 2 μg in TE buffer or equivalent
- Saliva (Oragene DNA OG-500 kit/OGD-500 or OG-575 & OGD-575)
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. Read more about our sample requirements here.
Anophthalmia and microphthalmia are rare developmental defects of the globe. Microphthalmia refers to an eye with reduced volume and may be associated with coloboma or with an orbital cyst. Anophthalmia is the absence of one or both eyes. Anophthalmia and microphthalmia may be unilateral or bilateral, and over 50% are associated with systemic abnormalities. Anophthalmia and microphthalmia may be inherited as an autosomal dominant, autosomal recessive, or X-linked manner. The major causative gene is SOX2 in which heterozygous loss-of-function variants account for 25% of cases. Examples of syndromes associated with anophthalmia/microphthalmia are CHARGE syndrome (CDH7) and COFS syndrome (ERCC2, ERCC5, ERCC6). Anterior segment dysgenesis (ASD) disorders encompass a wide variety of developmental conditions affecting the cornea, iris, and lens. It can be an isolated ocular anomaly or accompanied by systemic defects. Anterior segment anomalies are associated with an approximate 50% risk of glaucoma. The majority of genes associated with ASD show autosomal dominant inheritance. Axenfeld-Rieger syndrome is caused by variants in PITX2 and FOXC1 with an estimated prevalence of 1:200,000.
Genes in the Microphthalmia, Anophthalmia and Anterior Segment Dysgenesis Panel and their clinical significance
|ABCB6||Blood group, Langereis system, Pseudohyperkalemia, Dyschromatosis universalis hereditaria, Microphthalmia, isolated, with coloboma 7||AD/BG||9||20|
|ADAMTS18||Knobloch syndrome 2, Microcornea, myopic chorioretinal atrophy, and telecanthus, Retinal dystrophy, early onset, autosomal recessive||AR||4||14|
|ALDH1A3||Microphthalmia, isolated 8||AR||8||23|
|BCOR||Microphthalmia, syndromic, Oculofaciocardiodental syndrome||XL||40||53|
|BMP4||Microphthalmia, syndromic, Orofacial cleft||AD||8||39|
|BMP7||Anophthalmia, microphthalmia, and variable brain, ear, palate, and skeletal anomalies||AD||2||6|
|CHD7||Isolated gonadotropin-releasing hormone deficiency, CHARGE syndrome||AD||276||860|
|COL4A1||Schizencephaly, Anterior segment dysgenesis with cerebral involvement, Retinal artery tortuosity, Porencephaly, Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, Brain small vessel disease||AD||58||107|
|COX7B||Linear skin defects with multiple congenital anomalies 2||XL||5||5|
|CYP1B1||Glaucoma, primary open angle glaucoma, juvenile-onset, Glaucoma, primary open angle, adult-onset, Glaucoma, primary congenital, Peters anomaly||AR||24||237|
|ERCC2||Xeroderma pigmentosum, Trichothiodystrophy, photosensitive, Cerebrooculofacioskeletal syndrome 2||AR||26||98|
|ERCC5||Xeroderma pigmentosum, Xeroderma pigmentosum/Cockayne syndrome||AR||21||54|
|ERCC6*||Xeroderma Pigmentosum-Cockayne Syndrome, De Sanctis-Cacchione syndrome||AD/AR||87||135|
|FOXC1||Axenfeld-Rieger syndrome, Iridogoniodysgenesis, Peters anomaly||AD||46||135|
|FOXE3||Aphakia, congenital primary, Anterior segment mesenchymal dysgenesis, Cataract 34||AR/AD||9||29|
|FOXL2||Premature ovarian failure, Blepharophimosis, epicanthus inversus, and ptosis||AD||74||215|
|FREM1||Bifid nose, Manitoba oculotrichoanal syndrome, Trigonocephaly||AD/AR||14||35|
|FREM2||Fraser syndrome 2||AR||11||23|
|GJA1*||Oculodentodigital dysplasia mild type, Oculodentodigital dysplasia severe type, Syndactyly type 3||AD/AR||31||107|
|HCCS||Linear skin defects with multiple congenital anomalies 1 (MIDAS syndrome)||XL||7||13|
|HESX1||Septooptic dysplasia, Pituitary hormone deficiency, combined||AR/AD||15||26|
|MAB21L2||Microphthalmia/coloboma and skeletal dysplasia syndrome||AR||6||9|
|MFRP||Microphthalmia, isolated 5, Nanophthalmos 2, Retinitis pigmentosa, autosomal recessive||AR||27||30|
|MITF||Tietz albinism-deafness syndrome, Waardenburg syndrome, Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness (COMMAD)||AD/AR||32||58|
|NAA10||Microphthalmia, syndromic 1 (Lenz microphthalmia)||XL||16||10|
|NDP||Exudative vitreoretinopathy, Norrie disease||XL||31||167|
|OCRL||Lowe syndrome, Dent disease||XL||47||264|
|OTX2||Microphthalmia, syndromic, Pituitary hormone deficiency, combined, Retinal dystrophy, early-onset, and pituitary dysfunction||AD||23||73|
|PAX2||Isolated renal hypoplasia, Papillorenal syndrome, Focal segmental glomerulosclerosis 7||AD||30||96|
|PAX6||Aniridia, cerebellar ataxia, and mental retardation (Gillespie syndrome), Keratitis, Coloboma, ocular, Cataract with late-onset corneal dystrophy, Morning glory disc anomaly, Foveal hypoplasia, Aniridia, Optic nerve hypoplasia, Peters anomaly||AD||144||550|
|PITX2||Axenfeld-Rieger syndrome, Ring dermoid of cornea, Iridogoniodysgenesis, Peters anomaly||AD||23||101|
|PRSS56||Microphthalmia, isolated 6||AR||10||24|
|PXDN||Anterior segment dysgenesis 7||AR||7||14|
|RAB3GAP1||Warburg micro syndrome||AR||29||66|
|RARB||Microphthalmia, syndromic 12||AD/AR||9||6|
|RAX||Microphthalmia, isolated 3||AR||5||14|
|RBP4||Retinal dystrophy, iris coloboma, and comedogenic acne syndrome, Microphthalmia, isolated, with coloboma 10||AD/AR||8||7|
|SHH||Holoprosencephaly, Microphthalmia with coloboma||AD||42||218|
|SIX6||Microphthalmia, isolated, with cataract 2, Optic disc anomalies with retinal and/or macular dystrophy||AD||2||8|
|SLC38A8||Foveal hypoplasia 2||AR||11||18|
|SMCHD1||Facioscapulohumeral muscular dystrophy, Facioscapulohumeral muscular dystrophy, type 2||AD||51||79|
|SMOC1||Microphthalmia with limb anomalies||AR||9||15|
|STRA6||Microphthalmia, syndromic, Microphthalmia, isolated, with coloboma||AR||22||33|
|TENM3||Microphthalmia, isolated, with coloboma 10||AR||9||2|
|VSX2||Microphthalmia, isolated 2, Microphthalmia, isolated, with coloboma 3||AR||9||13|
* 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 Microphthalmia, Anophthalmia and Anterior Segment Dysgenesis Panel
|Gene||Genomic location HG19||HGVS||RefSeq||RS-number|
Assesses for non-coding disease-causing variants in one or more genes. For additional information, see the list of genes included in this panel.
- 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
- ~1,500 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
Due to one or more regions of segmental duplication, this panel has reduced sensitivity to detect variants in exon 1 of GJA1 and exon 1 of SOX2. 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. The technology may have limited sensitivity to detect variants in genes marked with these symbols (please see the Panel content table above).
- 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 (variant with a minor allele fraction of 14.6% is detected with 90% probability)
- 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 microphthalmia, anophthalmia and anterior segment dysgenesis panel covers classical genes associated with COFS syndrome, CHARGE syndrome, Axenfeld-Rieger syndrome, anophthalmia, anterior segment dysgenesis disorder, isolated anophthalmia – microphthalmia, microphthalmia, Peters anomaly and septo-optic dysplasia. 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 the following criteria are not Sanger confirmed: the variant quality score is above the internal threshold for a true positive call, and visual check-up of the variant at IGV is in-line with the variant call. 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.
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.