Case Study 03

Case Study 03

Case Studies
  • Gizem Özbek
  • August 12th 2021


Copy Number Variation (CNV) Analysis using NGS Cloud (Band Level)

The artificial intelligence-supported genetic data analysis platform NGS Cloud has reached molecular diagnosis due to its holistic CNV detection approach in an infant whose findings resemble a heterogenic genetic aetiology.

The diagnostic yield of whole-exome sequencing (WES) tests remains 25-40%, although there is a vast improvement in the last decade (1). Moreover, it takes 6 to 8 years for rare diseases to get an accurate diagnosis (2).  

We are living in an era where almost every day, clinical scientists establish a new gene-phenotype relation. It is crucial to keep all the utilised tools up-to-date, incorporating the latest and current literature knowledge and perform periodic reanalysis to increase the diagnostic yield of genetic data analyses. Moreover, this case study demonstrated that CNV variants, such as deletions and duplications, should be a standard part of the pipeline (3).

The Presentation:

A 2,5-month-old female with suspicion of CHARGE syndrome was referred for CHD7 single gene sequencing. She has unilateral aniridia, microphthalmos, unilateral chorioretinal/iris/lens coloboma, strabismus, microcephaly, posteriorly rotated ears, retrognathia, atrial septal defect, ventricular septal defect, proximal placement of hallux, respiratory distress, umbilical hernia, and unilateral renal agenesis. Due to the heterogeneity of the differential diagnostic list, the clinical team of Pairend decided to proceed with WES.

The Methods and the Findings:

The FASTQ files were uploaded to the NGS Cloud using PECULIAR (PairEnd Client UpLoad & Integrated Analysis Raw data). The clinical findings were entered as HPO (Human Phenotype Ontology) Terms (4). The HOPE (Harmonization of Ontologies by PairEnd)  prioritised the variants strongly associated with the given phenotype. In the last step, a heterozygous 3 Mb deletion in the critical region of DiGeorge Syndrome (22q11.2) within minutes by the automatic analysis algorithm, GENIUS (GENe Interactions Under Scope) (Figure 1).

Figure 1. The display of the CNV Result in NGS Cloud

The Result:

Nowadays, most cases (60-75%) remain unresolved after the first genetic analysis, and they can be diagnosed with a reanalysis (5). To overcome this challenge, we have built the modern data infrastructure of NGS Cloud that integrates advanced and up-to-date bioinformatics pipelines, automatic update of new publications, variants and other data points regarding gene-phenotype relationships with literature mining. Thus, it decreases the analysis time from hours to minutes, reducing manual data processing and, most importantly, more accurate clinical interpretation.


  1. Trujillano D et al (2017) Eur J Hum Genet. 2017;25(2):176‐182. doi:10.1038/ejhg.2016.146
  2. (Last Access Date: 24.05.2021)
  3. Frésard, L et al (2018) Cold Spring Harb Mol Case Stud., 4(6), a003392.
  4. Köhler S et al. (2019) Nucleic Acids Res. 2019;47(D1):D1018‐D1027. doi:10.1093/nar/gky1105
  5. Baker SW et al. (2019) J Mol Diagn. 2019;21(1):38‐48. doi:10.1016/j.jmoldx.2018.07.008
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Gizem Özbek August 12th 2021
Gizem Özbek August 12th 2021