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  • Test code: 05313
  • 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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Invitae Diamond-Blackfan Anemia Panel

Test description

The Invitae Diamond-Blackfan Anemia Panel analyzes genes associated with Diamond-Blackfan anemia (DBA). DBA is a genetically heterogeneous condition characterized by anemia, congenital malformations, growth restriction and an increased risk for leukemia and sarcoma. These genes were selected based on the available evidence to date to provide Invitae’s most comprehensive panel for DBA.

The primary panel includes 11 genes associated with DBA. In addition to the primary panel, clinicians can also choose to include 2 genes that have preliminary evidence of an association with DBA. These genes were selected from a review of the literature and expert recommendations. At this time, the association of these genes with DBA remains uncertain; however, some clinicians may wish to include genes that may prove to be clinically significant in the future. These genes can be added at no additional charge.

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.

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.

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Primary panel (11 genes)

GATA1 RPL11 RPL15 RPL26 RPL35A RPL5 RPS10 RPS19 RPS24 RPS26 RPS7

Add-on Preliminary-evidence Genes for Diamond-Blackfan Anemia (2 genes)

Genes with preliminary evidence of an association with Diamond-Blackfan anemia are available to add on to the primary panel. Adding on preliminary-evidence genes can increase the number of variants of uncertain significance that are identified. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

RPL19 RPS29

  • Diamond-Blackfan anemia (DBA)

DBA is a congenital hematological condition that is characterized by macrocytic anemia, reticulocytopenia and normocellular bone marrow with a deficiency of red cell precursors. While the phenotypic spectrum can be mild to severe, approximately 90% of individuals with DBA will have some hematologic symptoms within the first year of life. Congenital malformations, including craniofacial, upper limb, heart and genitourinary, are seen in approximately 50% of cases. Growth restriction is seen in ~30% of affected individuals. There is also an increased risk of developing acute myeloid leukemia, myelodysplastic syndrome and solid tumors, including osteogenic sarcoma. Individuals with the non-classic form may have mild or absent anemia, a later age of onset, congenital abnormalities, short stature with normal erythropoiesis, or may be phenotypically normal.

Pathogenic variants in these genes account for an estimated 55%–65% of individuals with DBA.

GeneAttribution to DBA
GATA1 rare
RPL5 ~7%
RPL11 ~5%
RPL15 rare
RPL26 rare
RPL35A ~3%
RPS7 ~1%
RPS10 ~6%
RPS19 ~25%
RPS24 ~2%
RPS26 ~3%

DBA is inherited in an autosomal dominant pattern except for GATA1-related DBA, which is X-linked.

Penetrance is incomplete.

The prevalence of DBA is estimated at 5–7 out of 1 million live births.

Testing for DBA 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
  • congenital anomalies that have been described in DBA
  • leukemia and solid tumors presenting at a younger age than usually found
  • a family history of DBA

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 the success rate varies based on sample quality. Please see our Sample requirements page for more details.

  1. Vlachos, A, et al. Clinical utility gene card for: Diamond-Blackfan anemia--update 2013. Eur. J. Hum. Genet. 2013; 21(10):None. PMID: 23463023
  2. 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
  3. 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
  4. Chen, S, et al. Diamond-blackfan anemia and growth status: the French registry. J. Pediatr. 2005; 147(5):669-73. PMID: 16291361
  5. Ohga, S, et al. Diamond-Blackfan anemia in Japan: clinical outcomes of prednisolone therapy and hematopoietic stem cell transplantation. Int. J. Hematol. 2004; 79(1):22-30. PMID: 14979474
  6. Sankaran, VG, et al. Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia. J. Clin. Invest. 2012; 122(7):2439-43. PMID: 22706301
  7. Quarello, P, et al. High frequency of ribosomal protein gene deletions in Italian Diamond-Blackfan anemia patients detected by multiplex ligation-dependent probe amplification assay. Haematologica. 2012; 97(12):1813-7. PMID: 22689679
  8. Wang, M, et al. Reduced expression of the mouse ribosomal protein Rpl17 alters the diversity of mature ribosomes by enhancing production of shortened 5.8S rRNA. RNA. 2015; 21(7):1240-8. PMID: 25995445
  9. Kuramitsu, M, et al. Extensive gene deletions in Japanese patients with Diamond-Blackfan anemia. Blood. 2012; 119(10):2376-84. PMID: 22262766
  10. Farrar, JE, et al. Ribosomal protein gene deletions in Diamond-Blackfan anemia. Blood. 2011; 118(26):6943-51. PMID: 22045982
  11. Landowski, M, et al. Novel deletion of RPL15 identified by array-comparative genomic hybridization in Diamond-Blackfan anemia. Hum. Genet. 2013; 132(11):1265-74. PMID: 23812780
  12. Clinton, C, Gazda, HT. Diamond-Blackfan Anemia. 2009 Jun 25. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301769
  13. Wlodarski, MW, et al. Recurring mutations in RPL15 are linked to hydrops fetalis and treatment independence in Diamond-Blackfan anemia. Haematologica. 2018; 103(6):949-958. PMID: 29599205
  14. Farrar, JE, et al. Exploiting pre-rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis. Am. J. Hematol. 2014; 89(10):985-91. PMID: 25042156
  15. Diamond Blackfan Anemia Foundation, Inc. http://dbafoundation.org/ Accessed September 2019.
  16. Diamond Blackfan Anemia Registry, http://www.dbar.org/ Accessed September 2019.

Recommendations for diagnosis and management of DBA were proposed at an international DBA clinical consensus conference:
PMID: 18671700

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.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
GATA1 NM_002049.3
RPL11 NM_000975.3
RPL15 NM_002948.3
RPL19 NM_000981.3
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
RPS29 NM_001032.4
RPS7 NM_001011.3