What is the Whole Genome Sequencing test?
The Whole Genome Sequencing test targets not only the protein-coding regions (exons) of the approximately 22,000 genes in the genome but also all introns and intergenic regions known to be associated with disease. It is a powerful diagnostic tool, providing a definitive diagnosis in ~21-59% of patients.
What is the difference between the whole genome sequencing (WGS) and whole exome sequencing (WES)?
- Whole Genome Sequencing analyzes all genetic information present in an individual’s entire genome. This includes the entire genomic region of the genes (exons and introns) and intergenic regions known to be associated with diseases.
- Whole Exome Sequencing sequences the entire exome. The exome is comprised of the regions within the genome that codes for proteins, called exons. It is estimated that the exome encompasses approximately only 1-2% of the genome, and contains approximately 85% of disease-causing pathogenic variants.
- The Whole Genome Sequencing test is a more comprehensive test than the Whole Exome Sequencing test and enables the laboratory to detect types of changes that whole exome sequencing cannot (e.g., copy number variations).
When is the Whole Genome Sequencing test useful?
Whole Genome Sequencing is useful when:
- The patient had a negative whole exome sequencing test.
- The patient’s symptoms or family history suggest a genetic etiology but does not correspond with a specific genetic disorder.
- The patient has symptoms of a well-defined genetic disorder that is caused by multiple genes (genetic heterogeneity) for which a multi-gene panel is not clinically available.
- The patient likely has a genetic disorder but previous clinical genetic testing did not yield a genetic diagnosis.
- The patient’s clinical presentation is unclear/atypical and there are multiple genetic conditions in the differential diagnosis.
How long does it take to get my patient’s results for the Whole Genome Sequencing test?
The turnaround time (TAT) is measured from sample receipt to delivery of the results report. This assumes that all required paperwork is completed fully and accurately at the time of sample submission. The TAT for the Whole Genome Sequencing test is 42 calendar days.
Documents needed are:
- Fully completed Requisition Form, including all billing information
- Fully completed Informed Consent Form. This includes the signatures of the patient and a physician.
Can I get my Whole Genome Sequencing results faster than the stated turnaround time (TAT)?
Arrangements may be made for results to be returned STAT if required for urgent medical management. Medical interpretation and report may be provided STAT within 10-12 calendar days after the sample has been sequenced. There is an additional charge for STAT orders. For pricing, please email PerkinElmer Genomics or call us at 1-866-354-2910. STAT testing can be ordered by checking the STAT box under the "Available Optional Testing Enhancements" Section on the Requisition Form.
STAT options include:
- D2010: STAT Whole Genome Sequencing, Proband ONLY
- D2020: STAT Whole Genome Sequencing, Proband ONLY - With StepOne® Biochemical Profile
- D2520: STAT Whole Genome Sequencing, Proband ONLY - DATA ONLY
- D2310: STAT Whole Genome Sequencing, TRIO
- D2320: STAT Whole Genome Sequencing, TRIO - With StepOne® Biochemical Profile
- D2530: STAT Whole Genome Sequencing, TRIO - DATA ONLY
Can I submit a sample for Whole Genome Sequencing without an order from a health care provider?
No, Whole Genome Sequencing must be ordered by a physician and results will only be reported to a physician.
What specimens are acceptable for Whole Genome Sequencing?
Strongly preferred sample types for Whole Genome Sequencing are dried blood spot (DBS), saliva, and whole blood (EDTA/purple top tube).
What is the price for the Whole Genome Sequencing test?
For pricing, please email PerkinElmer Genomics or call us at 866-354-2910.
Does PerkinElmer Genomics accept insurance or file for insurance directly?
At this time, PerkinElmer Genomics accepts only institution bill accounts or testing paid in-full by the patient at the time of testing.
Does PerkinElmer Genomics offer Whole Genome Sequencing without medical interpretation?
- Yes, we offer sequencing of the patient sample without medical interpretation.
- To obtain sequencing results only, please indicate on the Requisition Form. These testing options can be found on page 2.
- Sequencing only options include:
- D2500: Whole Genome Sequencing, Proband ONLY - DATA ONLY
- D2510: Whole Genome Sequencing, TRIO - DATA ONLY
- D2520: STAT Whole Genome Sequencing, Proband ONLY - DATA ONLY
- D2530: STAT Whole Genome Sequencing, TRIO - DATA ONLY
Does PerkinElmer Genomics offer reanalysis of Whole Genome Sequencing data and what is the cost?
- Yes, we offer reanalysis of genome data.
- We recommend waiting 6-12 months after the initial test was reported to allow additional curation of new research/clinical information.
- Turnaround time: 7-14 calendar days
- For pricing, please email PerkinElmer Genomics or call us at 1-866-354-2910.
How much of the genome is covered with the Whole Genome Sequencing test?
- The Whole Genome Sequencing test covers ~85% of the genome
- The Whole Genome Sequencing test covers >98% of all coding regions
Can we have access to the raw data? E.g., BAM, FastQ, VCF?
The raw data generated can be requested by the ordering health care provider.
What is reported in the Whole Genome Sequencing test?
- Variants that are known to be pathogenic or for which the laboratory has sufficient evidence suggesting pathogenicity in a gene that is suspected to cause the patient’s signs/symptoms.
- Predicted mutation(s) in a gene, which is potentially related to the phenotype but for which a specific clinical phenotype has not been previously well defined
- Variants of uncertain clinical significance in genes known to be associated with disease and genes not known currently associated with a disease (new genes) related to the patient’s phenotype.
- Variants that are pathogenic or for which the laboratory has sufficient evidence suggesting pathogenicity in a gene that is medically significant but unrelated to the patient’s presenting symptoms, unless the patient or parent/guardian declines this information.
Are there any genes/regions that will not be reported?
- A fraction (~10%) of the exome cannot be sequenced to accurately determine if a pathogenic variant is present. Therefore, pathogenic variants in these regions will not be detected by this analysis.
- The technology that sequences the Genome (i.e., next generation sequencing (NGS)) cannot accurately sequence repetitive regions, such as trinucleotide repeats. This means that NGS cannot provide data on regions such as the fragile X syndrome repeat region, the Huntington disease repeat region, or the myotonic dystrophy repeat region.
- Results from the Testing may indicate that additional testing, such as full gene sequencing to complete exons with poor coverage or deletion/duplication analysis, is recommended.
- Genetic changes identified may not necessarily predict the prognosis or severity of disease and it is possible that the genetic change may not affect management or treatment.
- Mitochondrial genome mutations, genes with pseudogenes, and epigenetic defects may not be detected by this test.
How does PerkinElmer Genomics handle reporting of incidental findings?
Adult patients and family members are given options in the informed consent form to indicate what type of results should be delivered. Options to opt-in for any of the following are provided:
- Pharmacogenetic variants: Pharmacogenetic variants are changes in the DNA that do not cause a disease but may be related to how your body processes certain medications, such as chemotherapy drugs, antipyretics, antidepressants, anticoagulants, and others. These variants may not be important to you if you are not taking the medications involved, but may tell you how well the medications will work or if you will have side effects if you do take the medications now or in the future.
- Carrier Status for Autosomal Recessive Conditions (ex. cystic fibrosis) A recessive condition is one in which two pathogenic variants in the same gene are required in order to show symptoms of the disease (one variant is inherited from each parent). Someone who has only one pathogenic variant does not show symptoms and is called a carrier. However, if we find a pathogenic variant in a recessive gene that is related to the patient's disease, we will report it as a diagnostic finding. Further testing may be necessary to look for a second pathogenic variant in that gene not identified by WES. You can choose whether or not you want us to report carrier status in genes that are not related to the patient's disease. The Testing is not designed to be a comprehensive carrier test. We are unable to guarantee that all conditions for which the individual is a carrier will be determined by the Testing. An individual may be a carrier for a condition in which there was little or no coverage in the Testing and therefore will not be detected. Additional carrier testing for reproductive purposes should be discussed with your doctor or genetic counselor.
- Diagnostic findings in adult onset medically-actionable disorders not related to disease: Medically-actionable conditions are those for which there is currently recommended treatment or preventative actions that can be taken to reduce the risk of developing the disease. An example would be hereditary cancer syndromes such as Lynch syndrome. We are unable to guarantee that the Testing will find all adult onset medically-actionable conditions for which the individual has a pathogenic variant. An individual may have a pathogenic variant for a condition in which there was little or no coverage in the Testing and therefore will not be detected. Additional testing for health purposes should be discussed with your doctor or genetic counselor.
- Diagnostic findings in adult onset currently medically non-actionable disorders not related to disease: Conditions that are not currently medically-actionable do not have recommended treatment or preventative measures. An example would be Alzheimer's disease. We are unable to guarantee that the Testing will find all adult onset medically non-actionable conditions for which the individual has a pathogenic variant. An individual may have a pathogenic variant for a condition in which there was little or no coverage in the Testing and therefore will not be detected. Additional testing for health purposes should be discussed with your doctor or genetic counselor.
Will PerkinElmer’s Whole Genome Sequencing test detect mitochondrial disease?
- Mitochondrial diseases can be caused by mutations in either the mitochondrial genome (a small circular chromosome found within the mitochondria) or by mutations in the nuclear genome (on the chromosomes found in the nucleus). Whole genome sequencing is typically done in such a way that only the exons in the nuclear genome are captured and fully sequenced, and thus, will identify most but not all of the mutations associated with mitochondrial disease.
- We are not capturing the entire mitochondrial genome as, with our experience, the yield is less than 1% and has low clinical utility.
- Our assay does, however, include common point mutations in the mitochondrial genome associated with diseases such as LHON, MERRF, and NARP.
- If you would like to discuss mitochondrial sequencing, please email PerkinElmer Genomics or call us at 1-866-354-2910 for more information.
Do you perform confirmation of mutations that are detected by the Whole Genome Sequencing test?
Can PerkinElmer Genomics detect single exon deletions and duplications?
Can PerkinElmer’s Whole Genome Sequencing test detect large rearrangements like multi-gene deletions and duplications?
What sequencing platform do we use for whole genome sequencing?
PerkinElmer Genomics uses the latest sequencing platforms from Illumina™. We utilize the NovaSeq™ to generate sequencing data for the Whole Genome Sequencing test.
How do I order sample collection kits?
- DBS collection packs can be ordered through customer service or via an email.
- Saliva or whole blood collection packs are currently not available. Once they become available they can be ordered in the same manner.