What is WES Test?

What is Whole Exome Sequencing (WES)?

Whole Exome Sequencing (WES) is an advanced genetic test that reads all protein-coding regions (exons) of the human genome in a single test. The human genome consists of approximately 3 billion base pairs, but protein-coding exonic regions cover only 1-2% of the genome. Despite this small region, approximately 85% of known disease-causing genetic variants are located in exonic regions.

WES has revolutionized the diagnosis of rare diseases. While traditional genetic tests examine genes one by one, WES scans ~20,000 genes at once, dramatically shortening the diagnostic process. Especially in patients with undiagnosed rare diseases, WES provides an additional diagnostic rate of 25-40%. (Whole Exome Sequencing — WES), insan genomunun tüm protein kodlayan bölgelerini (eksonlar) tek bir testte okuyan ileri düzey bir genetik testtir. İnsan genomu yaklaşık 3 milyar baz çiftinden oluşur, ancak protein kodlayan ekzom bölgeleri genomun yalnızca %1-2'sini kaplar. Bu küçük bölgeye rağmen, bilinen hastalığa neden olan genetik varyantların yaklaşık %85'i ekzom bölgelerinde yer alır.

At the Ministry of Health licensed Omega Genetik laboratory in Turkey, high-accuracy WES analysis is performed using the Illumina NovaSeq platform. Variants are classified by certified experts according to ACMG/AMP guidelines.

How Does WES Testing Work?

WES testing uses Next-Generation Sequencing (NGS) technology to read the protein-coding regions of DNA. The process consists of the following steps:

1. DNA Isolation: High-quality genomic DNA is isolated from a blood (EDTA tube) or saliva sample collected from the patient.
2. Exome Enrichment (Capture): DNA is fragmented and protein-coding exon regions are enriched by targeting them with thousands of specialized biotinylated oligonucleotide probes.
3. Sequencing: The enriched exome library is sequenced at high coverage depth (>100x mean coverage) on the Illumina NovaSeq 6000 platform.
4. Bioinformatics Analysis: Raw sequencing data (FASTQ) is first aligned to the reference genome (GRCh38/hg38) using BWA-MEM. Variants are then called using GATK. Variants are listed in a VCF file.
5. Variant Classification: Identified variants are evaluated according to ACMG/AMP 5-class criteria:
   • Class 1 — Benign: Not associated with disease
   • Class 2 — Likely benign: Most likely benign
   • Class 3 — VUS (Variant of Uncertain Significance): Cannot be interpreted, further research needed
   • Class 4 — Likely pathogenic: Most likely the disease cause
   • Class 5 — Pathogenic: Definitively causes the disease
6. Clinical Reporting: Classified variants are correlated with the patient's clinical presentation. A detailed clinical report signed by a certified medical genetics specialist is prepared.

Who Is WES Testing Suitable For?

WES testing may be recommended by a physician in the following situations:

WES Test Types

WES testing is applied in three main types according to different clinical needs:

1. Standard WES (Solo)

Only the patient's sample is analyzed. It is the most economical option. It is effective in diagnosing autosomal recessive and X-linked diseases.

2. Trio WES (Patient + Mother + Father)

In addition to the patient, WES analysis is performed on both parents. It is the most powerful method for identifying de novo variants. It traces the origin of familial variants, improves VUS interpretation, and significantly increases the diagnostic rate. It is the preferred approach especially in pediatric patients and rare disease diagnosis.

3. Rapid WES

Priority processing for urgent clinical situations. For neonatal intensive care patients and conditions requiring rapid intervention, results can be obtained in 2-3 weeks.

WES Test Process — Step by Step

The WES test process at Omega Genetik begins when the patient contacts us:

WES Test Accuracy Rate

WES testing covers approximately 85% of known disease-causing variants. However, it should be noted that it is not 100%. The limitations of WES are:

• Cannot fully analyze non-exonic (intronic/regulatory) regions
• Detection of large deletions/insertions (CNVs) is limited
• Cannot reliably detect triplet repeat sequences
• Cannot detect epigenetic changes
• Variants in newly undefined genes cannot be interpreted (VUS)

Despite all these limitations, WES is the most powerful single test currently available for rare disease diagnosis, and with proper clinical guidance, it achieves a high diagnostic rate.

WES or WGS?

Key differences between WES (Whole Exome Sequencing) and WGS (Whole Genome Sequencing):

In most clinical situations, WES is the preferred first-line test. WGS can be considered when WES results are negative and clinical suspicion persists.

WES Test Selection Criteria

WES test selection is determined by the following clinical factors:

• Test type: Solo, Trio, or Rapid WES
• CNV analysis: Additional deletion/duplication analysis
• Genetic counseling: Post-test counseling service
• Speed: Standard or priority (rapid) processing

Test selection is based on clinical indication and physician evaluation. Please contact us for the most suitable test option.

This page has been prepared by Omega Genetik experts. The content is for general informational purposes and does not replace medical advice. WES testing is performed only with physician referral.