Whole Exome Sequencing

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What is Whole Exome Sequencing?

A new form of genetic testing called Whole Exome Sequencing (WES) identifies changes in DNA by focusing on the most informative regions of the genome. The exome is the collection of those DNA sequences of the genes which determine the proteins, which your body needs in order to function properly. Most of the disease causing mutations that science has been able to pinpoint so far are located in exons. Whereas most genetic tests focus on a single gene or a set number of predetermined genes, WES tests examine thousands of genes simultaneously.

Which patients should be tested by Whole Exome Sequencing?

Patients who have already had genetic testing and do not yet have a definitive molecular diagnosis

Patients with a complex clinical phenotype or genetically very heterogeneous disorder that makes sequential testing cost-prohibitive.

Test reports

When an exome sequence is analyzed, it is compared to the reference human genome. While there are always certain variations, depending upon the individual and the data available, the reports usually contain genetic alterations linked to the clinical phenotype of the patient. Benign or likely benign variants are not reported.

Incidental findings

As the whole exome sequencing test is analyzing numerous different genes, there is a possibility for the recognition of incidental findings that are not necessarily related to the reason for ordering whole exome sequencing. These results may still be of medical importance for you and your family. In particular for the overview methods such as genome sequencing, incidental results can occur that relate to higher risks (that you may not be aware of) for potentially serious, unavoidable or non-treatable diseases. As part of the consent you can decide whether and under what circumstances you wish to be informed about such incidental findings.

We report incidental findings according to the ACMG guidelines (Green et al. 2013, GenMed 15:565) and we actively check the ACMG listed genes for reportable variants. In case of Trio analyses, incidental findings are only analysed for the index patient. Carrier information of the parents for identified incidental findings of the index can be requested with a new consent of the parents. Findings will be issued on individual reports. Incidental findings are not reported for fetal samples or samples from deceased persons.

Accuracy of reported findings

Our diagnostic NGS sequencing workflow has achieved an outstanding level of precision and accuracy. The evaluation of hundreds of performed Sanger confirmations showed a 100% accuracy of high quality NGS called variants. All variants which do not fulfill the quality parameters established for 100% accuracy are confirmed by Sanger sequencing.

Use of parental samples in the testing process of WES.

Biological parental samples are used to improve the interpretation of the final results in WES testing. In Trio analysis WES testing and bioinformatic analyses on parental samples is done in parallel to the analysis of the index patient. We check the parents/ material (based on the exome sequencing data) only with regard to the patient/s condition.

Limitations

WES testing does not target all exons within the human genome. Approx. 3% of the targeted exons may not be well covered due to insufficient coverage due to various technical reasons. Certain mutation types may not be detectable (for eg. large copy number variations, methylation, trinucleotide repeat expansions, etc.). The raw filtered variant may include secondary findings and variants that may be potential sequencing artefacts.

Test options

Exome Solo           70-100x sequencing depth (≥98% of targeted bases covered at ≥20x)

Exome Trio

Exome Solo + Copy Number Variation analysis (detects exon-level homozygous deletions, heterozygous deletions and homozygous duplications ≥ 3 subsequent exons)

Exome Solo + Mitochondrial genome analysis

Genesis Genoma Lab offers a thorough genetic counseling before the start of the genetic analysis and after receipt of the report, in order to answer all possible questions and explain to you in detail the results of the performed test and how these may affect you and your family.