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HelpTest Code WESPR Panel to Whole Exome Sequencing Reflex Test, Varies
Ordering Guidance
The American College of Medical Genetics and Genomics recommends that whole exome sequencing be considered as a first-tier or second-tier test for patients with one or more congenital anomalies, or developmental delay, or intellectual disability with onset prior to age 18 years.(1)
This test is only appropriate for patients who have had hereditary panel testing performed on a postnatal sample via next-generation sequencing (NGS) utilizing the Integrated DNA Technologies chemistry performed by Mayo Clinic Laboratories. To confirm that this test is possible for a specific patient, contact the laboratory at 800-533-1710.
If the patient has not had an appropriate test previously performed by Mayo Clinic Laboratories that can be reflexed but whole exome sequencing is desired, order either WESDX / Whole Exome Sequencing for Hereditary Disorders, Varies or WESMT / Whole Exome and Mitochondrial Genome Sequencing, Varies. If whole genome sequencing is desired, order WGSDX / Whole Genome Sequencing for Hereditary Disorders, Varies. A new specimen may be required.
This test is for affected patients (probands) only. It is possible to add family member comparators. For family member specimens being sent as comparators, order CMPRE / Family Member Comparator Specimen for Exome Sequencing, Varies. If WESPR is ordered on a family member comparator, this test will be canceled and CMPRE added as the appropriate test.
This test cannot support detection of deep intronic variants, trinucleotide repeat variants, or variants in the mitochondrial genome.
If separate mitochondrial genome testing is needed, order MITOP / Mitochondrial Full Genome Analysis, Next-Generation Sequencing (NGS), Varies
This test is not appropriate for identification of somatic variants in solid tumors. If this testing is needed, order MCSTP / MayoComplete Solid Tumor Panel, Next-Generation Sequencing, Tumor. A new specimen may be required.
This testing does not provide genotyping of patients for pharmacogenomic purposes. For an assessment for genes with strong drug-gene associations, order PGXQP / Focused Pharmacogenomics Panel, Varies. A new specimen may be required.
Targeted testing for familial variants (also called site-specific or known variant testing) is available for variants identified by this test. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.
Prenatal specimens (amniocentesis or chorionic villi) are not currently accepted for this test.
Additional Testing Requirements
Patient DNA is required to allow for confirmation of any new reportable variants, based on internal laboratory criteria. For most patients, stored DNA from the original panel test should be available for this testing. If a DNA sample is depleted or discarded, testing will proceed, however, a new sample will be requested from the ordering provider to attempt any necessary confirmatory testing. If a new sample is not provided, any findings that require confirmation will be reported with a disclaimer that confirmation was not performed due to lack of a DNA specimen.
To order whole exome sequencing for the patient and family member comparator specimens after a negative or inconclusive hereditary next-generation sequencing gene panel performed at Mayo Clinic Laboratories, perform the following steps:
1. Order WESPR / Panel to Whole Exome Sequencing Reflex Test, Varies
2. Call Mayo Clinic Laboratories at 800-533-1710 to request that the remaining DNA specimen be added to the WESPR order.
3. Complete the required paperwork and informed consent: Whole Exome Sequencing: Ordering Checklist.
4. Attach clinic notes from specialists relevant to patient's clinical features, if available.
5. Attach pedigree, if available.
6. If submitting family member comparator samples, order CMPRE / Family Member Comparator Specimen for Exome Sequencing, Varies for each family member.
 a. When available, the patient's biological mother and biological father are the preferred family member comparators.
 b. If one or both of the patient's biological parents are not available for testing, specimens from other first-degree relatives (siblings or children) can be used as comparators. Contact the laboratory at 800-533-1710 for approval to send specimens from other, non-first-degree relatives.
 c. The cost of analysis for family member comparator specimens is applied to the patient's (proband's) test. Family members will not be charged separately.
7. If needed, collect specimens. Label specimens with full name and birthdate. Do not label family members' specimens with the proband's name.
8. Send paperwork to the laboratory along with the specimens. If not sent with the specimen or if no specimen is being sent, fax a copy of the paperwork to 507-284-1759, Attn: WES Genetic Counselors.
For more information see Whole Exome and Genome Sequencing Information and Test Ordering Guide.
Necessary Information
Whole Exome Sequencing: Ordering Checklist is required. Fill out one form for the family and send with the specimens or fax to 507-284-1759, Attn: WES 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 exome 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. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube: Lavender top (EDTA) or yellow top (ACD)
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 4 days/Refrigerated 4 days/Frozen 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for samples received after 4 days and DNA yield will be evaluated to determine if testing may proceed.
2. 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: Cord blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Green top (sodium heparin)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for samples received after 4 days and DNA yield will be evaluated to determine if testing may proceed.
2. If a cord blood specimen is received, MATCC / Maternal Cell Contamination, Molecular Analysis, Varies will be performed at an additional charge.
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: Ambient (preferred) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection. Culture and/or extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. 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: Cultured fibroblasts
Source: Skin
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) <24 hours/Refrigerated <24 hours
Additional Information:
1. Specimens are preferred to be received within 24 hours of collection. Culture and/or extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.
2. 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: Blood spot
Supplies: Card-Blood Spot Collection (Filter Paper) (T493)
Container/Tube:
Preferred: Collection card (Whatman Protein Saver 903 Paper)
Acceptable: PerkinElmer 226 (formally Ahlstrom 226) filter paper or blood spot collection card
Specimen Volume: 2 to 5 Blood spots
Collection Instructions:
1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.
2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.
3. Do not expose specimen to heat or direct sunlight.
4. Do not stack wet specimens.
5. Keep specimen dry.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information:
1. Blood spot specimens are acceptable, but not recommended. Multiple extractions will be required to obtain sufficient yield for supplemental analysis, and there is significant risk for test failure due to insufficient DNA.
2. Due to lower concentration of DNA yielded from blood spot, it is possible that additional specimen may be required to complete testing.
3. For collection instructions, see Blood Spot Collection Instructions
4. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)
5. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Collection Kit (T786)
Specimen Volume: 1 Swab
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient (preferred) 30 days/Refrigerated 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.
Forms
1. Whole Exome Sequencing: Ordering Checklist is required.
2. New York Clients-Informed consent is required, included in the above form. Document on the request form or electronic order that a copy is on file.
Useful For
Serving as a second-tier test for patients in whom previous genetic testing was negative or inconclusive
Identifying causative variants in genes that were not included on panel testing which can allow for:
-Better understanding of the natural history/prognosis
-Targeted management (anticipatory guidance, management changes, specific therapies)
-Predictive testing of at-risk family members
-Testing and exclusion of disease in siblings or other relatives
-Recurrence risk assessment
Additionally, this testing may be useful in the context of a patient’s evolving clinical features.
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
| MATCC | Maternal Cell Contamination, B | Yes | No |
| G237 | Number of Comparators for WESPR | No | No |
Testing Algorithm
If a cord blood specimen is received, maternal cell contamination testing will be added and performed at an additional charge.
For skin biopsy or cultured fibroblast specimens, fibroblast culture will be performed at an additional charge. If viable cells are not obtained, the client will be notified.
Special Instructions
Method Name
Reanalysis of Whole Exome Next-Generation Sequencing (NGS) followed by Sanger Sequencing or Quantitative Polymerase Chain Reaction (qPCR), as needed
Reporting Name
Whole Exome Sequencing Panel ReflexSpecimen Type
VariesSpecimen Minimum Volume
See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
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) 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
-Secondary Findings: medically actionable variants unrelated to the indication for testing (see below for additional information)
-Previously Reported: variants that were reported on the original panel test report but do not reach the reporting criteria to be included in the above categories.
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.(5) 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 phenotype.
The presence of a variant in family member comparator specimens 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 reported for any family member.
Variants that are present in family members comparators but absent from the patient (proband) are not evaluated.
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 portions of the genes may not be adequately covered by this testing methodology.
Reanalysis and Raw Data Requests:
Patient data is not guaranteed to be stored indefinitely. Requests for reanalysis or release of raw data may not be possible, and a new whole exome 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.
Reanalysis of the patient's exome due to new patient clinical features, advances in genetic knowledge, or changes in testing methodology is available. See test WESR/ Whole Exome Sequencing Reanalysis, Varies or contact the laboratory at 800-533-1710 for more information.
Requests for the raw data obtained from whole exome 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. Clark MM, Stark Z, Farnaes L, et al. Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases. NPJ Genom Med. 2018;3:16. doi:10.1038/s41525-018-0053-8
2. 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
3. Tan NB, Stapleton R, Stark Z, et al. Evaluating systematic reanalysis of clinical genomic data in rare disease from single center experience and literature review. Mol Genet Genomic Med. 2020;8(11):e1508
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. 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
10 weeksPerforming Laboratory
Mayo Clinic Laboratories in Rochester
Test 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
81417-Patient only
81417, 81416-Patient and one family member comparator sample (duo) (as appropriate)
81417, 81416 x 2-Patient and two family member comparator samples (trio or non-traditional trio) (as appropriate)
81417, 81416 x 3-Patient and three family member comparator samples (quad) (as appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| WESPR | Whole Exome Sequencing Panel Reflex | 86205-2 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 621327 | Interpretation | 69047-9 |
| 621328 | Specimen | 31208-2 |
| 621329 | Source | 31208-2 |
| 621330 | Released By | 18771-6 |