DNA icon

Fanconi Anemia via the FANCM 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
3221 FANCM 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3221FANCM81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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 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 deficient 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.

Variants in FANCM have been reported to be associated with variable phenotypes, including primarily FA and increased risk for various cancers. One recent study provide data supporting a role for FANCM protein in azoospermia, which, given the role of Fanconi genes in providing genomic stability, seems quite plausible (Kasak et al. 2018. PubMed ID: 30075111). Biallelic variants in FANCM have been reported in patients with Fanconi anemia (Meetei et al. 2005. PubMed ID: 16116422; Harutyanyan et al. 2011. PubMed ID: 21681190; http://www.rockefeller.edu/fanconi/genes/) while more recently, a series of studies have shown that heterozygous variants in FANCM may be associated with increased risk for breast cancer (Kiiski et al. 2014. PubMed ID: 25288723; Peterlongo et al. 2015. PubMed ID: 26130695; Lhota et al. 2016. PubMed ID: 26822949). Pathogenic variants consist primarily of missense and protein truncating variants such as nonsense variants and small deletions resulting in premature protein termination. One large deletion encompassing exon 15 has also been reported in a patient with FA (Meetei et al. 2005. PubMed ID: 16116422). Variants in FANCM have been reported in only a few patients with FA (<1% of patients, Shimamura and Alter. 2010. PubMed ID: 20417588). FANCM protein is thought to have functional helicase and translocase activity that is required for proper recognition of DNA damage sites (Ciccia et al. 2007. PubMed ID: 17289582; Shimamura and Alter. 2010. PubMed ID: 20417588).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in the FANCM gene account for <1% of all Fanconi anemia (FA) cases (Auerbach. 2009. PubMed ID: 19622403; Shimamura and Alter. 2010. PubMed ID: 20417588).

Only one large deletion, which includes exon 15, has been reported for the FANCM gene (Meetei et al. 2005. PubMed ID: 16116422; The Rockefeller University Fanconi Anemia Mutation Database; Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the FANCM 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).

Indications for Test

Candidates are patients with clinical features of FA, individuals with a family history of FA, patients with early onset hematologic malignancies or solid tumors, and patients who 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 FANCM.

Gene

Official Gene Symbol OMIM ID
FANCM 609644
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Fanconi Anemia, Complementation Group M AR 614087

Related Tests

Name
Fanconi Anemia via the FANCC Gene
Fanconi Anemia via the FANCE Gene
Hereditary Breast and Ovarian Cancer - High Risk and Lynch Syndrome Panel
Hereditary Breast and Ovarian Cancer BRCA1/2 Panel
Hereditary Endometrial Cancer Panel
Melanoma Panel

Citations

  • Ameziane et al. 2015. PubMed ID: 26681308
  • Auerbach. 2009. PubMed ID: 19622403
  • Ciccia et al. 2007. PubMed ID: 17289582
  • Dokal. 2000. PubMed ID: 11030042
  • Faivre et al. 2000. PubMed ID: 11110674
  • Fanconi Anemia Research Fund, Inc.
  • Giampietro et al. 1997. PubMed ID: 8986277
  • Grompe and van de Vrught. 2007. PubMed ID: 17488615
  • Harutyunyan et al. 2011. PubMed ID: 21681190
  • Human Gene Mutation Database (Bio-base).
  • Kasak et al. 2018. PubMed ID: 30075111
  • Kiiski et al. 2014. PubMed ID: 25288723
  • Lhota et al. 2016. PubMed ID: 26822949
  • Meetei et al. 2005. PubMed ID: 16116422
  • Moldovan and D'Andrea. 2009. PubMed ID: 19686080
  • Peterlongo et al. 2015. PubMed ID: 26130695
  • Rosenberg et al. 2003. PubMed ID: 12393424
  • Rosenberg et al. 2011. PubMed ID: 21739583
  • Sasaki and Tonomura. 1973. PubMed ID: 4352739
  • Shimamura and Alter. 2010 PubMed ID: 20417588
  • Smogorzewska et al. 2007. PubMed ID: 17412408
  • The Rockefeller University Fanconi Anemia Mutation Database.
  • Tischkowitz and Hodgson. 2003. 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

loading Loading... ×

ORDER OPTIONS

An error has occurred while calculating the price. Please try again or contact us for assistance.

View Ordering Instructions

1) Select Test Method (Platform)


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.
Total Price: loading
Patient Prompt Pay Price: loading
A patient prompt pay discount is available if payment is made by the patient and received prior to the time of reporting.
Show Patient Prompt Pay Price
×
Copy Text to Clipboard
×