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Fanconi Anemia via the FANCD2 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11321 FANCD2 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11321FANCD281479 81479,81479 $990 Order Options and Pricing

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Siwu Peng, PhD

Clinical Features and Genetics

Clinical Features

Fanconi Anemia (FA) is an inherited anemia associated with bone marrow failure (aplastic anemia), however the clinical features of FA can expand well beyond hematologic anomalies. FA is characterized by a range of physical abnormalities, bone marrow failure (aplastic anemia), pancytopenia, and predisposition to cancers - particularly acute myelogenous leukemia (AML), gynecologic and GI tract cancers, and cancers of the head and neck (Auerbach 2009). FA patients are up to 800 fold more susceptible to AML than the general population with a median age of onset of 13 years (Rosenberg et al 2003). Physical abnormalities include radial ray defects (absent thumb or radius), skin pigmentation defects, short stature, microphthalmia, renal and urinary tract defects, genital defects (males in particular), gastrointestinal malformations (atresia), congenital heart disease, hearing and central nervous system defects, and general developmental delay (Tischkowitz and Hodgson 2003; Dokal 2000). About one-third of FA patients have no obvious physical abnormalities and are diagnosed only after a family member is diagnosed, or after developing hematologic anomalies such as thromobocytopenia, leukopenia, and anemia (Giampietro et al. 1997). A hallmark of FA is hypersensitivity of chromosomes to inter cross-strand linkage (ICL) agents such as diepoxybutane (DEB) or mitomycin C (MMC) (Sasaki and Tonomura 1973). Exposure of primary cell cultures from FA patients to DEB or MMC results in chromosomal aberrations (breaks, radials, rearrangements) due to damaged DNA repair mechanisms that require functional products of the Fanconi anemia genes. For example, the FANCA, -B, -C, -E, -F, -G, -L, and -M proteins are part of a nuclear core complex that regulates monoubiquitination of the FANCD2 and FANCI proteins (ID complex) during S-phase and after exposure to DNA crosslinking agents (Moldovan and D'Andrea 2009). In unaffected individuals, ubiquitination helps localize the ID complex to sites of DNA damage and facilitate repair (Grompe and van de Vrugt 2007; Smogorzewska et al. 2007), but in FA patients, this mechanism is impaired.

Genetics

FA is a genetically heterogeneous disorder. To date, 21 FA or FA-like genes have been discovered. Inheritance is primarily autosomal recessive or X-linked, however a case of heterozygous FA-like syndrome was associated with a dominant-negative variant in the RAD51 (FANCR) gene (Ameziane et al. 2015). Approximately 86% of all cases are attributed to variants in three genes: FANCA (~60%), FANCC (~16%) and FANCG (~10%) (Auerbach 2009). Since variants in FANCA are the most common cause of FA, it is important to note that large deletions make up over one-third of all reported pathogenic variants in FANCA. In the United States, the carrier frequency for Fanconi anemia is estimated at 1 in 181 and the incidence rate is estimated at 1 in 131,000 (http://www.fanconi.org/; Rosenberg et al. 2011). Nearly 95% of all FA cases are attributed to variants in eight genes, FANCA, -C, -G, -D1 (aka BRCA2), -D2, -E, -F, and –L that are either part of the core complex required for ID complex ubiquitination and facilitation of DNA repair or function directly in ICL recognition and repair (Grompe and van de Vrugt 2007). FA is phenotypically diverse even among related patients that harbor a common variant; null alleles however are reported to result in more severe phenotypes (Faivre et al. 2000). FA affects males and females roughly equally and affects all ethnic groups.

Clinical Sensitivity - Sequencing with CNV PGxome

Nearly 95% of all Fnconi Anemia cases are attributed to variants in eight genes, FANCA, -C, -G, -D1 (aka BRCA2), -D2, -E, -F, and –L that are either part of the core complex required for ID complex ubiquitination and facilitation of DNA repair or function directly in ICL recognition and repair (Grompe and van de Vrugt 2007). ~ 3-6% of FA patients are assigned to the FANCD2 complementation group (Kalb 2007; www.ncbi.nlm.nih.gov/). Gross deletions or duplications account for ~ 10% of the reported variants in the FANCD2 gene (www2.rockefeller.edu/fanconi/genes/).

Testing Strategy

Exons 12-28 of the FANCD2 gene share high sequence similarity with several other genomic regions outside of the FANCD2 gene (paralogs). In order to ensure we are sequencing exons 12-28 of the FANCD2 gene and not the paralogous regions, exons 12-28 are sequenced using Sanger sequencing and employing primers unique to the functional FANCD2 gene.

This test provides full coverage of all coding exons of the FANCD2 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

NOTE: Due to the presence of paralogous regions in the genome, exons 12-28 of the FANCD2 gene are difficult regions to cover using aCGH. Consequently, our aCGH test for the FANCD2 excludes exons 12-28.

Indications for Test

Patients with clinical features of FA, individuals with a family history of FA, and patients that develop aplastic anemia at any age even if they present no other physical abnormalities. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in FANCD2.

Gene

Official Gene Symbol OMIM ID
FANCD2 613984
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Fanconi Anemia, Complementation Group D2 AR 227646

Citations

  • Ameziane N. et al. 2015. Nature Communications. 6: 8829. PubMed ID: 26681308
  • Auerbach A.D. 2009. Mutation Research. 668: 4-10. PubMed ID: 19622403
  • Dokal I. 2000. Bailliere's Best Practice & Research. Clinical Haematology. 13: 407-25. PubMed ID: 11030042
  • Faivre L. et al. 2000. Blood. 96: 406470. PubMed ID: 11110674
  • Fanconi Anemia Research Fund, Inc.
  • Giampietro P.F. et al. 1997. American Journal of Medical Genetics. 68: 58-61. PubMed ID: 8986277
  • Grompe M., van de Vrugt H. 2007. Developmental Cell. 12: 661-2. PubMed ID: 17488615
  • Kalb R. et al. 2007. American Journal of Human Genetics. 80: 895-910. PubMed ID: 17436244
  • Moldovan G.L, D'Andrea A.D. 2009. Annual Review of Genetics. 43: 223-49. PubMed ID: 19686080
  • Rosenberg P.S. et al. 2003. Blood. 101: 822-6. PubMed ID: 12393424
  • Rosenberg P.S. et al. 2011. American Journal of Medical Genetics. Part A. 155A: 1877-83. PubMed ID: 21739583
  • Sasaki M.S., Tonomura A. 1973. Cancer Research. 33: 1829-36. PubMed ID: 4352739
  • Smogorzewska A. et al. 2007. Cell. 129: 289-301. PubMed ID: 17412408
  • The Rockefeller University Fanconi Anemia Mutation Database
  • Tischkowitz M.D., Hodgson S.V. 2003. Journal of Medical Genetics. 40: 1-10. PubMed ID: 12525534

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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View Ordering Instructions

1) Select Test Method (Platform)


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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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