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  • Test code: 05311
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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  1. Test Catalog
  2. Invitae Fanconi Anemia Panel

Invitae Fanconi Anemia Panel

Test description

The Invitae Fanconi Anemia test analyzes 17 genes associated with Fanconi anemia (FA), which is characterized by progressive bone marrow failure, physical abnormalities, and increased risk of malignancy.

Genetic testing of these genes may establish or confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also allow for testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

If the patient has undergone a bone marrow transplant prior to genetic testing or currently has a hematological malignancy with actively circulating tumor cells, testing a sample type that is not derived from blood (such as skin biopsy) is warranted. While we do not accept this sample type directly, we can accept DNA derived from skin or muscle, though deletion/duplication analysis is not guaranteed for DNA samples because the success rate varies based on sample quality. Please see our Specimen requirements page for more details.

Genes tested

BRCA2 BRIP1 ERCC4 FANCA FANCB FANCC FANCD2 FANCE FANCF FANCG FANCI FANCL FANCM PALB2 RAD51C SLX4 XRCC2

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Primary panel (17 genes)

BRCA2 BRIP1 ERCC4 FANCA FANCB FANCC FANCD2 FANCE FANCF FANCG FANCI FANCL FANCM PALB2 RAD51C SLX4 XRCC2

Panel details and technical assay limitations

Clinical information

  • Fanconi anemia (FA)

Fanconi anemia (FA) is a multisystemic disorder primarily characterized by progressive bone marrow failure leading to low blood cell counts (pancytopenia). Associated symptoms may include, anemia due to lack of red blood cells (erythropenia), immunodeficiency due to lack of white blood cells (leukopenia), and failure to clot due to lack of platelets (thrombocytopenia). Affected individuals also typically present with a variable spectrum of physical abnormalities and exhibit developmental delay. FA predisposes individuals to developing several types of cancers, including acute myeloid leukemia and solid tumors of the head and neck, esophagus, and genital tract.

Pathogenic variants in this gene list account for more than 95% of reported Fanconi anemia cases. The most common genes are FANCA, FANCC, and FANCG, and pathogenic variants in these genes cumulatively represent approximately 85-90% of FA patients. The BRCA2, BRIP1, FANCB, FANCD2, FANCE, and FANCF genes combined account for 10%, while the remaining FA genes represent less than 5% of cases.

FA is predominantly inherited in an autosomal recessive manner except for pathogenic variants in FANCB, which are inherited in an X-linked manner.

The major clinical features of FA include physical abnormalities, progressive bone marrow failure, and cancer susceptibility. However, there is variable expressivity as some individuals with FA do not present with any physical abnormalities or bone marrow failure.

  • Physical abnormalities present in 60%-75% of affected individuals.
  • Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. By age 40 to 50 years, the estimated cumulative incidence of bone marrow failure is 90%.
  • The incidence of hematologic malignancies, primarily acute myeloid leukemia, is 10%-30%. The incidence of solid tumors, particularly of the head and neck, skin, GI tract, and genital tract, is 25%-30%.

The prevalence of FA is approximately 1 in 100,000 to 1 in 200,000 live births. The carrier frequency is estimated to be 1 in 181, with a higher rate in some ethnic backgrounds.

Testing for FA should be considered in:

  • individuals with any clinical features of FA
  • anyone developing aplastic anemia at any age
  • individuals who develop cancers of the head and neck, gynecologic system or gastrointestinal system (squamous cell carcinoma or adenocarcinoma) at an early age
  • individuals with family history of FA

If the patient has undergone a bone marrow transplant prior to genetic testing or currently has a hematological malignancy with actively circulating tumor cells, testing a sample type not derived from blood (such as skin biopsy) is warranted. While we do not accept this sample type directly, we can accept gDNA derived from skin or muscle. However, deletion/duplication analysis is not guaranteed for gDNA samples, as success rate varies based on sample quality. Please see our Sample requirements page for more details. for more detail.

  1. Alter, BP, Kupfer, G. Fanconi Anemia. 2002 Feb 14. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1401/ PMID: 20301575
  2. Shimamura, A, Alter, BP. Pathophysiology and management of inherited bone marrow failure syndromes. Blood Rev. 2010; 24(3):101-22. doi: 10.1016/j.blre.2010.03.002. PMID: 20417588
  3. Alter, BP, et al. Malignancies and survival patterns in the National Cancer Institute inherited bone marrow failure syndromes cohort study. Br. J. Haematol. 2010; 150(2):179-88. doi: 10.1111/j.1365-2141.2010.08212.x. PMID: 20507306
  4. Rosenberg, PS, et al. How high are carrier frequencies of rare recessive syndromes? Contemporary estimates for Fanconi Anemia in the United States and Israel. Am. J. Med. Genet. A. 2011; 155A(8):1877-83. PMID: 21739583
  5. Hays L, et al, eds. Fanconi Anemia: Guidelines for Diagnosis and Management. 4th ed. Eugene, OR: Fanconi Anemia Research Fund, Inc. http://fanconi.org/index.php/publications/guidelines_for_diagnosis_and_management. Accessed September 2015.
  6. Rosenberg, PS, et al. How high are carrier frequencies of rare recessive syndromes? Contemporary estimates for Fanconi Anemia in the United States and Israel. Am. J. Med. Genet. A. 2011; 155A(8):1877-83. doi: 10.1002/ajmg.a.34087.

Recommendations for diagnosis and management of FA have been proposed:
Hays L, et al, eds. Fanconi Anemia: Guidelines for Diagnosis and Management. 4th ed. Eugene, OR: Fanconi Anemia Research Fund, Inc. http://fanconi.org/index.php/publications/guidelines_for_diagnosis_and_management.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Assay notes

If the patient has undergone a bone marrow transplant prior to genetic testing or currently has a hematological malignancy with actively circulating tumor cells, testing a sample type not derived from blood (such as skin biopsy) is warranted. While we do not accept this sample type directly, we can accept gDNA derived from skin or muscle. However, deletion/duplication analysis is not guaranteed for gDNA samples, as success rate varies based on sample quality. Please see our Sample requirements page for more details. for more detail.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
BRCA2* NM_000059.3
BRIP1 NM_032043.2
ERCC4 NM_005236.2
FANCA NM_000135.2
FANCB NM_001018113.1
FANCC NM_000136.2
FANCD2* NM_033084.3
FANCE NM_021922.2
FANCF NM_022725.3
FANCG NM_004629.1
FANCI NM_001113378.1
FANCL NM_018062.3
FANCM NM_020937.2
PALB2 NM_024675.3
RAD51C NM_058216.2
SLX4 NM_032444.2
XRCC2 NM_005431.1

BRCA2: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
FANCD2: Deletion/duplication analysis is not offered for exons 14-17 and 22.

Clinical resources
Genes and associated cancers chart Hematology gene list Hereditary cancer gene list Hereditary cancer risks and references chart Invitae brochure
Patient resources
Patient guide: Genetic testing for hereditary cancer Patient guide: Genetic testing simplified Patient guide: Hereditary breast cancer Patient guide: Hereditary colorectal cancer
Test information
Forms page Specimen requirements page

References

  1. Alter, BP, Kupfer, G. Fanconi Anemia. 2002 Feb 14. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1401/ PMID: 20301575
  2. Alter, BP, et al. Malignancies and survival patterns in the National Cancer Institute inherited bone marrow failure syndromes cohort study. Br. J. Haematol. 2010; 150(2):179-88. doi: 10.1111/j.1365-2141.2010.08212.x. PMID: 20507306
  3. Hays L, et al, eds. Fanconi Anemia: Guidelines for Diagnosis and Management. 4th ed. Eugene, OR: Fanconi Anemia Research Fund, Inc. http://fanconi.org/index.php/publications/guidelines_for_diagnosis_and_management. Accessed September 2015.
  4. Rosenberg, PS, et al. How high are carrier frequencies of rare recessive syndromes? Contemporary estimates for Fanconi Anemia in the United States and Israel. Am. J. Med. Genet. A. 2011; 155A(8):1877-83. PMID: 21739583
  5. Rosenberg, PS, et al. How high are carrier frequencies of rare recessive syndromes? Contemporary estimates for Fanconi Anemia in the United States and Israel. Am. J. Med. Genet. A. 2011; 155A(8):1877-83. doi: 10.1002/ajmg.a.34087.
  6. Shimamura, A, Alter, BP. Pathophysiology and management of inherited bone marrow failure syndromes. Blood Rev. 2010; 24(3):101-22. doi: 10.1016/j.blre.2010.03.002. PMID: 20417588

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