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Test Catalog

Test ID: BRAJ3    
BRCA1/BRCA2 Ashkenazi Jewish 3-Site Mutation Panel, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Establishing a diagnosis of hereditary breast and ovarian cancer (HBOC) in patients of Ashkenazi Jewish ancestry

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test utilizes targeted next-generation sequencing to detect the 3 Ashkenazi Jewish founder mutations, c.68_69delAG and c.5266dupC in BRCA1, and c.5946delT in BRCA2. These are also well-known by their previous nomenclature: c.185delAG and c.5385insC in BRCA1, and c.6174delT in BRCA2. Sanger sequencing may also be performed to confirm detected variants. Analysis is performed for the 3 Ashkenazi Jewish mutations only. This assay does not rule out presence of other mutations within BRCA1 or BRCA2.

 

Note: Analysis of the area surrounding the three Ashkenazi Jewish variants may be required in the performance of this assay, which could result in identification of additional variants. Contact the laboratory at 800-533-1710 with any questions regarding assay performance.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Hereditary breast and ovarian cancer (HBOC) is an autosomal dominant hereditary cancer syndrome associated with germline mutations in the BRCA1 or BRCA2 genes. Mutations within these 2 genes account for the majority of hereditary breast and ovarian cancer families. HBOC is predominantly characterized by young-onset breast cancer and ovarian cancer. However, HBOC is also associated with increased risks for prostate cancer, pancreatic cancer, fallopian tube cancer, and male breast cancer. HBOC is highly penetrant; the risk for developing an invasive breast cancer is about 60% to 65% and the risk for developing ovarian cancer is about 40% by age 70. Some individuals develop multiple primary or bilateral cancers. The National Comprehensive Cancer Network and the American Cancer Society provide recommendations regarding the medical management of individuals with HBOC.

 

There are founder mutations in BRCA1 and BRCA2 described in several populations including the Dutch, Icelandic, and Ashkenazi Jewish populations. The 3 common founder mutations in the Ashkenazi Jewish population are c.68_69delAG and c.5266dupC in BRCA1, and c.5946delT in BRCA2. These are listed according to current Human Genome Variation Society guidelines; however, these are also well-known by their previous nomenclature: c.185delAG and c.5385insC in BRCA1, and c.6174delT in BRCA2. The overall prevalence of the BRCA1/2 founder mutations in the Ashkenazi Jewish population is 1 in 40. Per the National Comprehensive Cancer Network, women of Ashkenazi Jewish ancestry who have been diagnosed with breast or ovarian cancer should be considered for testing for the 3 common founder mutations (www.nccn.org).

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

 

All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical Correlations:

This assay will not detect all of the mutations that cause hereditary breast and ovarian cancer (HBOC). Therefore, the absence of a mutation does not eliminate the possibility of a diagnosis of HBOC. For predictive testing, it is important to first document the presence of a BRCA1 or BRCA2 gene mutation in an affected family member.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete. We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.

 

Technical Limitations:

The methodology used for this assay is targeted next-generation sequencing; therefore, analysis of mutations outside of the 3 Ashkenazi Jewish founder mutations is not performed. If a diagnosis is still suspected, consider full gene sequencing using AJADD (BRCA1/BRCA2 Full Gene Add On) to assess for mutations and large deletions outside of the 3 Ashkenazi Jewish founder mutations.

 

Note: Analysis of the area surrounding the familial variant may be required in the performance of this assay, which could result in identification of additional variants. Call 800-533-1710 with any questions regarding assay performance.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Richards CS, Nazneen A, 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 May;17(5):405-424

2. Petrucelli N, Daly MB, Feldman GL. Hereditary Breast and Ovarian Cancer due to Mutations in BRCA1 and BRCA2. Genet Med. 2010 May;12(5):245-259

3. BRCA1 and BRCA2 Hereditary Breast and Ovarian Cancer-GeneReviews-NCBI Bookshelf. Accessed 12/14/16. Available at

www.ncbi.nlm.nih.gov/books/NBK1247/

4. Lindor NM, McMaster ML, Lindor CJ, et al: Concise Handbook of Familial Cancer Susceptibility Syndromes. Second Edition. J Natl Cancer Inst Monogr 2008;(38):1-93

5. Saslow D, Boetes C, Burke W, et al: American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007 Mar-Apr;57(2):75-89

6. Chen S, Parmigiani G: Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 2007 Apr 10;25(11):1329-1333

7. Janavivius R. Founder BRCA1/2 Mutations in Europe: implications for hereditary breast-ovarian cancer prevention and control. EPMA J. 2010 Sept;1(3):397-412

Special Instructions Library of PDFs including pertinent information and forms related to the test