Home
HelpTest ID: WGSR Whole Genome Sequencing Reanalysis, Varies
Ordering Guidance
This test is only appropriate for patients who have previously had WGSDX / Whole Genome Sequencing for Hereditary Disorders, Varies performed by Mayo Clinic Laboratories.
This test is for affected patients (probands) only. This test does not need to be ordered for family member comparators (CMPRG / Family Member Comparator Specimen for Genome Sequencing, Varies).
Additional Testing Requirements
DNA specimens from the patient (proband) and all family member comparators included in the original whole genome sequencing test are required to allow for confirmation of any new reportable variants, based on internal laboratory criteria. For most patients, stored DNA from the original whole genome sequencing test should be available for this testing.
To use stored DNA for this test:
Order WGSR / Whole Genome Sequencing Reanalysis, Varies. By calling Mayo Clinic Laboratories at 800-533-1710 to request that this test be added on to the remaining DNA specimen for the patient (proband). The laboratory will determine if there is sufficient DNA remaining for the proband and all comparators to perform confirmation of any new results. If there is sufficient DNA, the order will proceed.
If the patient and/or family member comparators are found to have an insufficient quantity of stored DNA, follow the instructions below:
1. If there is not sufficient DNA remaining for the patient (proband): If an order for WGSR was already placed in the steps above, the order will be canceled, and the client notified of the test cancellation. Collect a new proband specimen and order WGSR for the new specimen.
2. If there is not sufficient DNA remaining for one or more family member comparators: For the family members who were included as comparators in the original whole genome sequencing test but do not have sufficient stored DNA, collect new comparator specimens and order CMPRG / Family Member Comparator Specimen for Genome Sequencing, Varies for the new specimens.
For more information see Whole Exome and Genome Sequencing Information and Test Ordering Guide.
Shipping Instructions
Specimens are preferred to arrive within 96 hours of collection.
Necessary Information
Whole Genome Sequencing: Ordering Checklist is required for all patients. Complete the following sections on pages 2 through 4:
Patient (Proband) Information
Reason for Testing: provide reason for reanalysis request
Provide new information in:
-Patient (Proband) Suspected Diagnoses
-Patient (Proband) Clinical Evaluations
-Patient (Proband) Clinical Features
Attach clinic notes and pedigree with any relevant new clinical or family history information.
Fax the paperwork, clinic notes, and pedigree to 507-284-1759, Attn: WGS Genetic Counselors.
Specimen Required
For most patients, a new specimen submission will not be required. Testing can be performed using stored DNA from the original whole genome sequencing test. To order testing on the stored specimen, see Additional Testing Requirements.
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information: To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.
Specimen Type: Skin biopsy
Supplies: Fibroblast Biopsy Transport Media (T115)
Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.
Specimen Volume: 4-mm punch
Specimen Stability Information: Refrigerated (preferred)/Ambient
Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.
Â
Specimen Type: Cultured fibroblast
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.
Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)
Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Swab Collection Kit (T786)
Specimen Volume: 1 Swab
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient 30 days
Additional Information: Due to lower quantity/quality of DNA yielded from saliva, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.
Specimen Type: Muscle tissue biopsy
Supplies: Muscle Biopsy Kit (T541)
Collection Instructions: Prepare and transport specimen per instructions in Muscle Biopsy Specimen Preparation Instructions.
Specimen Volume: 10 to 80 mg
Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated
Forms
1. Whole Genome Sequencing: Ordering Checklist is required.
2. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:
Useful For
Identifying a diagnosis or additional variants associated with the phenotype in patients who previously have had a negative or inconclusive whole genome sequencing test
Reanalyzing whole genome sequencing data when a patient (proband) presents with new clinical features
Reanalyzing whole genome sequencing data to pick up newly discovered gene-disease associations, changes to variant classification, and bioinformatics pipeline upgrades
Genetics Test Information
Whole genome sequencing utilizes next-generation sequencing to detect single nucleotide variants, small insertions and deletions, copy number variants, mitochondrial genome variants, and select repeat expansion variants throughout the genome. In patients who have had negative or inconclusive whole genome sequencing results, reanalysis of previously generated whole genome sequencing data has the potential to identify additional variants associated with the patient's phenotype and increase the diagnostic yield of this testing.
This test is available for patients who previously had WGSDX / Whole Genome Sequencing for Hereditary Disorders, Varies performed by Mayo Clinic Laboratories and would like reanalysis of the results.
It is recommended to wait at least 1 year after the original whole genome sequencing test results were released to request reanalysis unless there are substantial changes to the patient's phenotype.(1)
This test may be ordered by the provider who ordered the original whole genome sequencing test or by a new provider if the patient is currently under their care. If this test is ordered by a new provider, results will be sent only to the new provider. The provider who ordered the original whole genome sequencing test will receive an amended report stating that the original whole genome sequencing results are no longer current.
Method Name
Reanalysis of Whole Genome Next-Generation Sequencing followed by Sanger Sequencing, Quantitative Polymerase Chain Reaction (qPCR), or other methods, as needed
Reporting Name
Whole Genome Sequencing ReanalysisSpecimen Type
VariesSpecimen Minimum Volume
Whole blood: 1 mL; Other specimen types: See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Ambient (preferred) | ||
| Frozen | |||
| Refrigerated | |||
Clinical Information
Whole genome sequencing utilizes next-generation sequencing technology to assess the genome of patients with suspected underlying genetic disorders. Based on a meta-analysis, the diagnostic utility of whole genome sequencing is approximately 41%.(2)
In patients who have had negative or inconclusive whole genome sequencing results, reanalysis of whole genome sequencing data has been found to result in a new diagnosis in approximately 10% of cases.(3)
For more information, see Whole Exome Sequencing (WGS): Questions and Answers for Providers.
Reference Values
An interpretive report will be provided.
Interpretation
Variants of interest are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(4,5) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Variants are reported in one of the following categories:
-Likely Causative: Variants with a high degree of suspicion for causing the patient's reported clinical features
-Possibly Relevant: Variants that may be related to the patient's clinical features or variants in genes of uncertain significance (GUS)
-Secondary Findings: Medically actionable variants unrelated to the indication for testing (see below for additional information)
It is possible that a variant may not be recognized as the underlying cause of disease due to incomplete scientific knowledge about the function of all genes in the human genome or the impact of variants in those genes.
Secondary Findings:
Patients are evaluated for medically actionable secondary findings and these findings are reported in accordance with the most current ACMG recommendations, including the most up-to-date gene list.(6) Variants in these genes will not be evaluated or reported if the patient opts out of this evaluation unless they overlap with the patient's reported clinical features.
The opt in or opt out selection from the original whole genome sequencing test will be maintained unless a new Informed Consent form is returned denoting a change in this selection. If the patient originally opted in to receive secondary findings and a secondary finding was originally reported, the status cannot be changed to opt out.
The presence of a secondary finding in family member comparator samples is stated on the patient's (proband's) report unless family members opt out of secondary findings. If the patient (proband) opts out, secondary findings will not be evaluated or reported in any family member comparators. Secondary findings that are present in family members comparators but absent from the patient (proband) are not evaluated or reported.
The absence of a reportable secondary finding does not guarantee that there are no disease-causing or likely disease-causing variants in these genes, as review is limited to known or highly suspected pathogenic findings, and not all regions of these genes are adequately evaluated by this technology.
Reanalysis and Raw Data Requests:
It is not guaranteed that patient data will be stored indefinitely. Requests for reanalysis or release of raw data may not be possible, and a new whole genome sequencing order may be required if the original patient data is no longer available or no longer compatible with current bioinformatics processes or analysis tools.
Requests for the raw data obtained from whole genome sequencing should be directed to the laboratory. A separate fee may apply. Raw data will be released for individuals who complete a Mayo Clinic release of information form. If raw data for family member comparators is requested, it will only be released with an accompanying request for the proband's raw data. Contact the laboratory for instructions on completing the release of information form. The laboratory is not responsible for providing software or other tools needed to visualize, filter, or interpret this data.
Clinical Reference
1. Deignan JL, Chung WK, Kearney HM, et al. Points to consider in the reevaluation and reanalysis of genomic test results: a statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2019;21(6):1267-1270
2. Clark MM, Stark Z, Farnaes L, et al. Meta-analysis of the diagnostic and clinical utility of genome and genome sequencing and chromosomal microarray in children with suspected genetic diseases. NPJ Genom Med. 2018;3:16. doi:10.1038/s41525-018-0053-8
3. Costain G, Jobling R, Walker S, et al. Periodic reanalysis of whole-genome sequencing data enhances the diagnostic advantage over standard clinical genetic testing. Eur J Hum Genet. 2018;26(5):740-744. doi:10.1038/s41431-018-0114-6
4. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424
5. Riggs ER, Andersen EF, Cherry AM, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) [published correction appears in Genet Med. 2021 Nov;23(11):2230]. Genet Med. 2020;22(2):245-257. doi:10.1038/s41436-019-0686-8
6. Miller DT, Lee K, Gordon AS, et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23(8):1391-1398. doi:10.1038/s41436-021-01171-4
Day(s) Performed
Varies
Report Available
84 daysTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
First reanalysis: No charge
81427-For all subsequent reanalysis requests
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| WGSR | Whole Genome Sequencing Reanalysis | 86206-0 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 618564 | Interpretation | 69047-9 |
| 618565 | Specimen | 31208-2 |
| 618566 | Source | 31208-2 |
| 618567 | Released By | 18771-6 |
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
Testing Algorithm
Skin biopsy or cultured fibroblast specimens:
If a skin biopsy is received, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.
mcl-moltechtestmenu; mcl-exomegenomeseq; mcl-neurology