Neurofibromatosis Type 2 via the NF2 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
118 NF2$910.00 81406 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity
This test detects mutations in ~ 73% of patients with an established family history of NF2 and ~ 60% of sporadic cases (Evans et al. J Med Genet 44:424-428, 2007).  Somatic mosaicism is likely to account for the lower mutation detection rate in patients with sporadic NF2 (Evans et al. Am J Hum Genet 63:727-736, 1998).

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 NF2$690.00 81405 Add to Order
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Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Features
Neurofibromatosis Type 2 (NF2, OMIM 101000) is a tumor predisposition syndrome with bilateral vestibular schwannoma (BVS) as the hallmark.  Patients with NF2 may also develop schwannoma at other locations and other tumors such as meningioma, glioma, neurofibroma, astrocytoma and skin tumors.  Posterior subcapsular lens opacities are common in NF2.  Other common symptoms include hearing loss, imbalance, tinnitus, facial weakness and headache (Parry et al. Am J Med Genet 52:450-461, 1994; Kanter et al. Neurology 30:851-859, 1980).  Two clinical subtypes are recognized.  A severe subtype, also called the Wishart subtype, is characterized by an early onset, severe features, rapid progression, and predisposition to meningioma and spinal tumors, in addition to the BVS.  A mild subtype, also known as Gardner subtype, has a later onset, a comparatively benign course, and a low incidence of meningioma and spinal tumors (Bruder et al. Hum Mol Genet 10:271-282, 2001).  NF2 is a panethnic disease with an incidence of approximately 1 in 56,000 live births (Evans et al. Am J Med Genet A 152A:327-332, 2010).
Mutations in the NF2 gene cause NF2 (Trofatter et al. Cell 72:791-800, 1993; Rouleau et al. Nature 363:515-521, 1993).  In about half of cases, NF2 is inherited as an autosomal dominant trait, with high penetrance.  In the remaining half, NF2 is caused by de novo mutations (Evans et al. J Med Genet 29:841-846, 1992).  About 25 % of patients with sporadic NF2 are mosaic (Evans et al. Am J Hum Genet 63:727-736, 1998; Kluwe et al. J Med Genet 40:109-114, 2003).  To date, about 400 NF2 germline mutations were reported.  Nonsense and frameshift mutations represent the majority of mutations and have been associated with the severe NF2 subtype.  However, somatic mosaicism of such mutations may result in milder phenotype.  Missense mutations, small in-frame insertions or deletions, and gross deletions have been associated with the milder phenotype (Selvanathan. Clin Genet 77(2):163-170, 2010).  Splicing mutations have been associated with phenotypic variability, including intrafamilial variability (Kluwe et al. Am J Med Genet 77:228-33, 1998).  NF2 encodes the Merlin protein, a tumor-suppressor.
Testing Strategy
This test involves bidirectional Sanger sequencing of all coding exons and splice sites of the NF2 gene.  The full coding sequence of each exon plus ~10 bp of flanking DNA on either side are sequenced. We will also sequence any single exon (Test #100) in family members of patients with a known mutation or to confirm research results.
Indications for Test
Patients presenting with a clinical diagnosis of NF2 according to the NIH criteria and presymptomatic testing of family members in NF2 families with known mutations.


Official Gene Symbol OMIM ID
NF2 607379
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Neurofibromatosis, Type 2 101000

Related Test

Familial Meningioma via the SMARCE1 Gene


Genetic Counselors
  • Bruder, C. E., (2001). "High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH." Hum Mol Genet 10(3): 271-82. PubMed ID: 11159946
  • Evans, D. G., (1992). "A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity." J Med Genet 29(12): 841-6. PubMed ID: 1479598
  • Evans, D. G., (1998). "Somatic mosaicism: a common cause of classic disease in tumor-prone syndromes? Lessons from type 2 neurofibromatosis." Am J Hum Genet 63(3): 727-36. PubMed ID: 9718334
  • Evans, D. G., (2007). "Mosaicism in neurofibromatosis type 2: an update of risk based on uni/bilaterality of vestibular schwannoma at presentation and sensitive mutation analysis including multiple ligation-dependent probe amplification." J Med Genet 44(7): 424-8. PubMed ID: 17307835
  • Kanter, W. R., (1980). "Central neurofibromatosis with bilateral acoustic neuroma: genetic, clinical and biochemical distinctions from peripheral neurofibromatosis." Neurology 30(8): 851-9. PubMed ID: 6774282
  • Kluwe L, Mautner V, Heinrich B, Dezube R, Jacoby LB, Friedrich RE, MacCollin M. 2003. Molecular study of frequency of mosaicism in neurofibromatosis 2 patients with bilateral vestibular schwannomas. Journal of medical genetics 40: 109–114. PubMed ID: 12566519
  • Parry, D. M., (1994). "Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity." Am J Med Genet 52(4): 450-61. PubMed ID: 7747758
  • Rouleau, G. A., (1993). "Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2." Nature 363(6429): 515-21. PubMed ID: 8379998
  • Selvanathan et al. Further genotype--phenotype correlations in neurofibromatosis 2. Clin Genet. 77(2):163-70, 2010. PubMed ID: 19968670
  • Trofatter, J. A., (1993). "A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor." Cell 72(5): 791-800. PubMed ID: 8453669
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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