Invitae Bone Marrow Failure Syndromes Panel

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  • Test code: 05301
  • 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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Test description

The Invitae Bone Marrow Failure Syndromes Panel analyzes 39 genes that are associated with hereditary bone marrow failure. Many of these genes are also associated with disorders that typically present with other hematological and physical findings.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide 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 gDNA derived from skin or muscle, though deletion/duplication analysis is not guaranteed for gDNA samples because the success rate varies based on sample quality. Please see our Sample requirements page for more details.

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Primary panel (39 genes)

BRCA2 BRIP1 CTC1 DKC1 ELANE ERCC4 FANCA FANCB FANCC FANCD2 FANCE FANCF FANCG FANCI FANCL FANCM GATA1 GATA2 MPL NHP2 NOP10 PALB2 RAD51C RPL11 RPL26 RPL35A RPL5 RPS10 RPS19 RPS24 RPS26 RPS7 RUNX1 SLX4 TERC TERT TINF2 WAS XRCC2

BRCA2: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
FANCD2: Deletion/duplication analysis is not offered for exons 14-17.
GATA2: Analysis includes the intronic variant NM_032638:c.1017+572C>T.

  • congenital amegakaryocytic thrombocytopenia (CAMT)
    • congenital amegakaryoctyic thrombocytopena II (CAMTII)
  • Diamond-Blackfan anemia (DBA)
  • dyskeratosis congenita
    • Hoyeraal-Hreidarsson syndrome
    • Revesz syndrome
    • Coats plus syndrome
  • ELANE-related neutropenia
    • cyclic neutropenia
    • severe congenital neutropenia
  • familial platelet disorder with propensity to myeloid malignancy (FPD/AML)
  • Fanconi anemia (FA)
  • GATA2 deficiency
    • familial myelodysplastic (MDS)/acute myeloid leukemia (AML) syndrome
    • Emberger syndrome
    • immunodeficiency-21 (IMD21)
    • monocytopenia and mycobacterial infection (MonoMAC)
  • WAS-related disorders
    • Wiskott-Aldrich syndrome
    • X-linked thrombocytopenia (XLT)
    • X-linked severe congenital neutropenia

Inherited bone marrow failure syndromes (IBMFS) are a group of rare multisystemic disorders characterized by abnormal bone marrow production. Bone marrow contains the stem cells that go on to develop into the various cell types found in blood. Some IBMFS affect more than one cell type (i.e., red cells, platelets, and white cells), while other IBMFS only affect one cell type. IBMFS typically have additional hematological symptoms present, such as anemia and thrombocytopenia. All of the conditions in this panel have an increased risk of developing cancer—either hematological or solid tumors. The actual risk of developing a cancer is dependent upon in which gene a pathogenic variant is found. Many of these conditions have additional physical characteristics present, but the overlap of symptoms can make establishing a specific diagnosis difficult.

This panel consists of a diverse set of genetic disorders that are characterized by abnormal bone marrow production. The clinical phenotypes are highly variable and much broader than previously recognized. Additional information about each disorder is available by following the links below to their respective condition’s page.

ConditionInheritanceInitial hematologic findingsOther clinical features
Fanconi anemia AR aplastic anemia physical abnormalities, developmental delay, increased risk for leukemia and solid tumors
Dyskeratosis congenita AD, AR, X-linked aplastic anemia nail dystrophy, abnormal skin pigmentation, oral leukoplakia, increased risk of leukemia, solid tumors, pulmonary fibrosis
Diamond-Blackfan anemia AD, X-linked anemia congenital malformations, growth retardation, increased risk of MDS/leukemia and solid tumors
ELANE-related neutropenia AD neutropenia recurrent fever, omphalitis, skin and oropharyngeal inflammation, cervical adenopathy, infections
Congenital amegakaryocytic thrombocytopenia AR thrombocytopenia cardiac defects, cerebral and cerebellar hypoplasia, developmental delay
Familial platelet disorder with propensity to myeloid malignancy AD thrombocytopenia increased risk of MDS/leukemia, mild-to-moderate bleeding tendency
WAS-related disorders X-linked thrombocytopenia intermittent bleeding, recurrent infections, autoimmune disorders, eczema, immune dysfunction

The inheritance pattern of IBMFS varies depending on the gene:

  • DBA – Autosomal dominant, X-linked (GATA1 only)
  • DC – Autosomal dominant, autosomal recessive, X-linked
  • FA – Autosomal recessive, X-linked (FANCB only)
  • WAS – X-linked recessive
  • GATA2 – Autosomal dominant
  • RUNX1 – Autosomal dominant
  • CAMT – Autosomal recessive
  • ELANE – Autosomal dominant

The prevalence varies depending upon the disorder that is diagnosed. Though they are all rare, the three most common types of IBMFS on this panel are: Fanconi anemia (approximately 1 in 100,000 to 1 in 200,000 live births), WAS-related disorders (1 in 100,000 to 1 in 1,000,000), and Diamond-Blackfan anemia (5-7 in 1,000,000 live births). Other disorders tested by this panel are even rarer or have an unknown prevalence.

Testing for IBMFS should be considered in individuals with a personal and/or family history of:

  • macrocytic anemia with no significant cytopenia
  • reticulocytopenia
  • normocellular bone marrow with small amounts of erythroid precursors
  • decreased or progressive bone marrow failure at any age
  • myelodysplastic syndrome or acute myelogenous leukemia
  • solid tumors of the head, neck, or anogenital area in individuals who are younger than 50 years of age
  • anyone developing aplastic anemia at any age
  • individuals who, at an early age, developed cancers of the head and neck, gynecologic system, or gastrointestinal system (squamous cell carcinoma or adenocarcinoma)
  • profound thrombocytopenia (<70,000 platelets/mm2) and small platelet size
  • persistent neutropenia
  • lymphoma
  • arrested development of the bone marrow
  • MDS/AML
  • thrombocytopenia

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 gDNA derived from skin or muscle, but deletion/duplication analysis is not guaranteed for gDNA samples because success rate varies based on sample quality. Please see our Sample requirements page for more details.

  1. 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
  2. Fernández, García, MS, Teruya-Feldstein, J. The diagnosis and treatment of dyskeratosis congenita: a review. J Blood Med. 2014; 5:157-67. PMID: 25170286
  3. Geddis, AE. Congenital amegakaryocytic thrombocytopenia. Pediatr Blood Cancer. 2011; 57(2):199-203. PMID: 21337678
  4. 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.
  5. Mir, MA, et al. Spectrum of myeloid neoplasms and immune deficiency associated with germline GATA2 mutations. Cancer Med. 2015; 4(4):490-9. PMID: 25619630
  6. Owen, CJ, et al. Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy. Blood. 2008; 112(12):4639-45. PMID: 18723428
  7. 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
  8. Vlachos, A, et al. Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference. Br. J. Haematol. 2008; 142(6):859-76. PMID: 18671700
  9. Vlachos, A, et al. Incidence of neoplasia in Diamond Blackfan anemia: a report from the Diamond Blackfan Anemia Registry. Blood. 2012; 119(16):3815-9. PMID: 22362038

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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
BRCA2* NM_000059.3
BRIP1 NM_032043.2
CTC1 NM_025099.5
DKC1 NM_001363.4
ELANE NM_001972.2
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
GATA1 NM_002049.3
GATA2* NM_032638.4
MPL NM_005373.2
NHP2 NM_017838.3
NOP10 NM_018648.3
PALB2 NM_024675.3
RAD51C NM_058216.2
RPL11 NM_000975.3
RPL26 NM_000987.3
RPL35A NM_000996.2
RPL5 NM_000969.3
RPS10 NM_001014.4
RPS19 NM_001022.3
RPS24 NM_033022.3
RPS26 NM_001029.3
RPS7 NM_001011.3
RUNX1 NM_001754.4
SLX4 NM_032444.2
TERC NR_001566.1
TERT NM_198253.2
TINF2 NM_001099274.1
WAS NM_000377.2
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.
GATA2: Analysis includes the intronic variant NM_032638:c.1017+572C>T.