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Fanconi Anemia via the FANCC Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7047 FANCC 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7047FANCC81479 81479,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

Turnaround Time

18 days on average for standard orders or 13 days 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 also characterized by a range of physical abnormalities, pancytopenia, and predisposition to certain cancers - particularly acute myelogenous leukemia (AML), gynecologic and GI tract cancers, and cancers of the head and neck (Auerbach. 2009. PubMed ID: 19622403). 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. PubMed ID: 12393424). 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. PubMed ID: 12525534; Dokal. 2000. PubMed ID: 11030042). 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. PubMed ID: 8986277).

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. PubMed ID: 4352739). 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. PubMed ID: 19686080). In unaffected individuals, ubiquitination helps localize the ID complex to sites of DNA damage and facilitate repair, but in FA patients, this mechanism is impaired (Grompe and van de Vrugt. 2007. PubMed ID: 17488615; Smogorzewska et al. 2007. PubMed ID: 17412408).

Genetics

FA is a genetically heterogeneous disorder. To date, 22 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. PubMed ID: 26681308). Approximately 86% of all cases are attributed to variants in three genes: FANCA (~ 60%), FANCC (~ 16%), and FANCG (~ 10%) (Auerbach. 2009. PubMed ID: 19622403). 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. PubMed ID: 21739583). 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. PubMed ID: 17488615). FA is phenotypically diverse even among related patients that harbor the same variants; null alleles however are reported to result in more severe phenotypes (Faivre et al. 2000. PubMed ID: 11110674). FA affects males and females roughly equally and affects all ethnic groups.

To date, over 75 unique causative variants have been reported throughout the FANCC gene comprising primarily missense/nonsense variants and numerous small deletions (primarily frameshift). Unlike FANCA, large deletions involving the FANCC gene are not a frequent cause of FA. A small number of variants in FANCC account for ~ 90% of reported pathogenic variants: c.67delG (c.322delG), p.Arg185*, p.Arg548*, and an intronic variant c.456+4A>T (IVS4+4A>T). The intronic variant IVS4+4A>T is found at a high frequency among the Ashkenazi Jewish and Japanese populations and is reported to result in milder phenotypes in Japanese FA patients than in Ashkenzi Jewish FA patients (Futaki et al. 2000. PubMed ID: 10666230). The carrier frequency of IVS4+4A>T is estimated at ~ 1 in 90 in Ashkenzi Jews (Verlander et al. 1995. PubMed ID: 7492758; Whitney et al. 1993. PubMed ID: 8348157) and may correlate with a more severe form of FA marked by a high frequency of birth defects and early onset of hematologic disease and leukemia (Gillio et al. 1997. PubMed ID: 9207444).

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in the FANCC gene ccount for ~ 16% of all Fanconi Anemia (FA cases) (Auerbach. 2009. PubMed ID: 19622403).

Gross deletions and duplicatoins in the FANCC gene are an infrequent cause of FA, and few gross deletions and duplications have been reported for the FANCC gene (The Rockefeller University Fanconi Anemia Mutation Database; HGMD Professional 2018.1).

Testing Strategy

This test provides full coverage of all coding exons of the FANCC gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Patients with clinical features of FA, individuals with a family history of FA, and patients that develop aplastic anemia and hematologic disorders 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 FANCC.

Gene

Official Gene Symbol OMIM ID
FANCC 613899
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Fanconi Anemia, Complementation Group C AR 227645

Citations

  • Ameziane et al. 2015. PubMed ID: 26681308
  • Auerbach. 2009. PubMed ID: 19622403
  • Dokal. 2000. PubMed ID: 11030042
  • Faivre et al. 2000. PubMed ID: 11110674
  • Fanconi Anemia Research Fund, Inc.
  • Futaki et al. 2000. PubMed ID: 10666230
  • Giampietro et al. 1997. PubMed ID: 8986277
  • Gillio et.al. 1997. PubMed ID: 9207444
  • Grompe and van de Vrught. 2007. PubMed ID: 17488615
  • Human Gene Mutation Database (Bio-base).
  • Moldovan and D’Andrea. 2009. PubMed ID: 19686080
  • Rosenberg et al. 2003. PubMed ID: 12393424
  • Rosenberg et al. 2011. PubMed ID: 21739583
  • Sasaki and Tonomura. 1973. PubMed ID: 4352739
  • Smogorzewska et al. 2007. PubMed ID: 17412408
  • The Rockefeller University Fanconi Anemia Mutation Database.
  • Tischkowitz and Hodgson. 2003. PubMed ID: 12525534
  • Verlander et.al. 1995. PubMed ID: 7492758
  • Whitney et al. 1993. PubMed ID: 8348157

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


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


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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