The entire coding sequences (exons plus 20 bp upstream and 20 bp downstream of each coding exon) of the targeted genes are captured, sequenced using NGS and aligned to the human reference genome. A minimum NGS coverage of 20X for all coding exons is achieved. Variants in the targeted regions that are of potential clinical significance, based on the ACMGG guidelines for interpretation of sequence variants (Richards et al. Genet Med 17(5):405-524, 2015), will be reported. Copy number variation is assessed by coverage depth within the targeted regions compared to a normalized set of controls. Copy number variants within the targeted regions that are of potential clinical significance will also be reported. Specific PCR amplifications are used to detect Alu repeat insertions within BRCA1 exon 10, and BRCA2 exons 3, 22, and 25. All reported variants of potential clinical significance will be confirmed by a different technology or platform.
Targeted NGS BRCA1 and BRCA2 sequencing and deletion/duplication analysis is use for the detection of germline pathogenic variants in patients at increased risk for breast, ovarian, prostate, or pancreatic cancer. Germline mutations in the BRCA1 and/or BRCA2 genes are associated with an increased risk for these cancers. Incomplete penetrance as well as variable expressivity, variable age of onset and a wide-range of risk estimate have been reported in multiple families with BRCA1 and BRCA2 germline mutations (Levy-Lahad et al. Proc Natl Acad Sci 98:3232-3236, 2001; Antoniou et al. Am J Hum Genet 82:937-948, 2008). The lifetime risk for an individual with a pathogenic germline mutation in BRCA1 or BRCA2 has been estimated to be 40-80% for breast cancer and 11-40% for ovarian cancer. See http://www.ncbi.nlm.nih.gov/books/NBK1247/ for additional information.
Interpretive report provided
This assay will not detect intronic mutations outside the region sequenced in the BRCA1 and BRCA2 genes or mutations in other genes associated with these diseases will not be identified.
Collect specimen in a lavender top tube. Send intact specimen within 24 hours if stored at room temperature or within 5 days if stored refrigerated. Include the patient's family history, pedigree, and ethnicity on the test requisition. Obtaining informed consent from the patient prior to genetic testing is strongly recommended. If desired, a UMHS Request and Consent for Genetic Testing form can be obtained from the MMGL Molecular Genetics Laboratory by contacting the MLabs Client Services Center at 800-862-7284 or online at https://mlabs.umich.edu/sites/default/files/2020-01/file/pci-mmgl_infor….
Most insurance carriers require prior authorization for payment. BRCA testing will not begin until insurance prior authorization is received by the MMGL Laboratory or it has been confirmed that prior authorization is not required. It is the obligation of the ordering health care provider to obtain prior authorization before testing can begin. To obtain BCN prior authorization call Joint Venture Hospital Laboratories (JVHL) at 800-445-4979; for all others insurances, contact the plan directly. By ordering this test the clinician acknowledges that informed consent 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.