Test Code BAP1Z BAP1-Tumor Predisposition Syndrome, BAP1 Full Gene Analysis, Varies

Ordering Guidance

For a comprehensive hereditary renal cancer gene panel that includes testing for BAP1, consider RENCP / Hereditary Renal Cancer Panel, Varies.

Testing for the BAP1 gene as part of a customized panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

Targeted testing for familial variants (also called site-specific or known mutations testing) is available for this gene. For more information see FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required

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.

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) 4 days/Refrigerated

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Molecular Genetics: Inherited Cancer Syndromes Patient Information Sheet (T519)

3. If not ordering electronically, complete, print, and send a Oncology Test Request (T729) with the specimen.

Secondary ID

614581

Useful For

Evaluating patients with a personal or family history suggestive of BAP1-tumor predisposition syndrome (BAP1-TPDS)

Establishing a diagnosis of BAP1-TPDS allowing for targeted cancer surveillance based on associated risks

Identifying genetic variants associated with increased risk for BAP1-TPDS, allowing for predictive testing and appropriate screening of at-risk family members

Special Instructions

Method Name

Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

Reporting Name

BAP1 Full Gene Analysis

Specimen Type

Varies

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type	Temperature	Time	Special Container
Varies	Varies

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Germline variants in the BAP1 gene are associated with BAP1-tumor predisposition syndrome (BAP1-TPDS), a rare autosomal dominant hereditary cancer syndrome.(1) BAP1-TPDS is characterized by increased risk to develop a variety of tumors, including BAP1-inactivated melanocytic tumor (also known as atypical Spitz tumor, or "BAPoma"), uveal and cutaneous melanoma, malignant mesothelioma, and renal cell carcinoma.(1) Many other tumor types, including basal cell carcinoma, hepatocellular carcinoma, cholangiocarcinoma, and meningioma, have also been associated with this syndrome.(1-6)

While the true penetrance of BAP1-TDPS is unknown due to both its rarity and ascertainment bias in the existing data, studies have shown up to 88% of individuals with an identified variant had a cancer diagnosis.(1,2)

Management and surveillance guidelines have been proposed by several multi-disciplinary expert groups.(1,5)

Reference Values

An interpretive report will be provided.

Interpretation

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(7) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Method Description

Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of the BAP1 gene, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletions-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction (PCR)-based quantitative method is performed to test for the presence of deletions and duplications in the BAP1 gene.

There may be regions of the BAP1 gene that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. The reference transcript for BAP1 gene is NM_004656.4. Reference transcript numbers may be updated due to transcript re-versioning. Always refer to the final patient report for gene transcript information referenced at the time of testing.(Unpublished Mayo method)

Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

Day(s) Performed