Test Overview
The entire CFTR gene is sequenced with Illumina sequencing by synthesis (SBS) chemistry, using the Illumina DNA PCR-Free Tagmentation based whole genome sequencing (WGS) library preparation. Sequences are mapped and aligned to genome reference consortium human build 38 (GRCh38, hg38); variants are called by Illumina DRAGEN germline pipeline and analyzed with the assistance of Illumina Emedgene tertiary analysis pipeline. Average depth of coverage is ≥30x. A minimum sequencing depth of 10x is achieved for all coding regions (+/-15 bp). Regions not meeting these depth metrics are further assessed by either Sanger sequencing or manual review. Pathogenic or likely pathogenic variants, based on the ACMG/AMP guidelines (PMID: 25741868) and ClinGen specifications (clinicalgenome.org/working-groups/sequence-variant-interpretation), and pathogenic or likely pathogenic copy number variants, based on the ACMG/ClinGen standards (PMID: 31690835), are reported. Variants of uncertain clinical significance (VUS) are only reported if specifically requested from the ordering provider following genetic counseling of the screened individual. All reported variants not meeting the quality criteria are confirmed by an orthogonal technology.
This pan-ethnic CFTR carrier screening assay utilizes a whole genome sequencing (WGS) platform to sequence the entire CFTR gene. It identifies and reports all pathogenic and likely pathogenic (P/LP) variants. This includes comprehensive coverage of the 100 minimal sequence variants recommended by the American College of Medical Genetics and Genomics (ACMG) in the latest 2023 guidelines, achieving a carrier detection rate of at least 95% across all major US ethnic populations (PMID: 37310422). Furthermore, it expands diagnostic capability by detecting additional CFTR pathogenic sequence variants and copy number variants (CNVs). This assay is intended for reproductive carrier screening in individuals of any ethnic background, with or without a known family history of cystic fibrosis, to precisely define reproductive carrier risk.
Reference ranges may change over time. Please refer to the original patient report when evaluating results. Interpretive report provided.
* Reference ranges may change over time. Please refer to the original patient report when evaluating results.
Minimum depth coverage metrics do not apply to regulatory elements or deep intronic regions of the targeted gene; consequently, variants in those regions may not be reliably detected. Balanced structural variants are generally not analyzed. Furthermore, variants outside of the targeted gene are not analyzed. This analysis may not reliably detect mosaicism or CNV in regions with pseudogene interference. Variant classification is based on current scientific knowledge and is subject to change. Test interpretation may be affected by the presence of hematologic malignancies or allogeneic transplants. Because this screen does not detect all pathogenic variants nor report variants without established pathogenicity, a negative result significantly reduces, but does not eliminate, the risk of being a carrier. Reproductive risk is also dependent on the carrier status of the individual’s partner.
Test Details
14-28 days
- CFTR
- Carrier Screening
- Carrier Screen
Specimen Requirements
Collect blood specimen in a EDTA lavender top tube. Send it within 24 hours if stored at room temperature or within 5 days if stored refrigerated. Fill out a MLabs Molecular test requisition (or place an e-order if applicable): https://mlabs.umich.edu/media/166 Fill out a Clinical History Form for Insurance Prior Authorization (include all required documentation indicated at the bottom of this form): https://mlabs.umich.edu/sites/default/files/2020-08/file/mlab11618clini… Fill out a UMHS Request and Consent for Genetic Testing form: https://mlabs.umich.edu/sites/default/files/2023-04/file/germline-conse… Michigan State law requires the ordering provider to obtaining informed consent from the patient prior to prognostic or predictive genetic testing. Contact a MLabs Client Services Center at 800-862-7284 to request paper copies or to setup a client account.
Please refer to "Cystic Fibrosis (CF) Carrier Screening (non-blood)" for alternate specimen types.
5 mL whole blood
1 mL whole blood
Additional Information
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Most insurance carriers require prior authorization for genetic testing. Testing will not begin until insurance prior authorization is received by the laboratory or it is confirmed that prior authorization is not required. The ordering health care provider can obtain the prior authorization or request the laboratory to submit it. To obtain BCN prior authorization call Joint Venture Hospital Laboratories (JVHL) at 800-445-4979; for all other insurances, contact the plan directly. By ordering this test the clinician acknowledges that informed consent, https://mlabs.umich.edu/sites/default/files/2023-04/file/germline-conse…, has been obtained from the patient as required by applicable state or federal laws and the ordering clinician has authorization from the patient permitting MLabs to report the test results to the ordering clinician. Test includes medical geneticist interpretation of results billed as a separate additional charge. This test is not available without interpretation. |