• Test code: 08111
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

Invitae Agammaglobulinemia Panel

Test description

The Invitae Agammaglobulinemia Panel analyzes up to 31 genes that are associated with agammaglobulinemia or hypogammaglobulinemia. Genetic testing of these genes is useful to confirm a diagnosis in patients who are suspected of having agammaglobulinemia or hypogammaglobulinemia from clinical symptoms and laboratory findings. This includes recurrent bacterial infections occurring at an early age, small or absent tonsils and lymph nodes on physical examination and very low levels of immunoglobulins and B cells in serum. Identification of disease-causing variants provide accurate risk assessment and carrier status for at -risk relatives.

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Primary panel (6 genes)


Add-on Hypogammaglobulinemia Genes (5 genes)

GATA2 deficiency, MOGS-congenital disorder of glycosylation (CDG-IIb), X-linked lymphoproliferative disorder, and TRNT1 can all cause hypogammaglobulinemia. Given the clinical overlap between patients with agammaglobulinemia and hypogammaglobulinemia, analyzing these genes may be appropriate. These genes can be included at no additional charge.


Add-on Common Variable Immunodeficiency Genes (20 genes)

Patients with CVID can have immunoglobulin levels that look similar to agammaglobulinemia or hypogammaglobulinemia. Given the clinical overlap between patients with agammaglobulinemia or hypogammaglobulinemia and CVID, analyzing these genes may be appropriate. These genes can be included at no additional charge.


Alternative tests to consider

For a broader analysis of genes associated with primary immunodeficiency:

Gene Disorder Protein name Protein symbol
BLNK BLNK deficiency B-cell linker protein BLNK
BTK BTK deficiency Bruton agammaglobulinemia tyrosine kinase BTK
CD79A Igα deficiency immunoglobulin-associated alpha Ig-alpha
CD79B Igβ deficiency immunoglobulin-associated beta Ig-beta
IGLL1 λ5 deficiency lambda-5 IGL5
PIK3R1 PI3KR1 deficiency, PI3KR1 loss of function p85-alpha protein p85-alpha

Clinical subtypes
Agammaglobulinemia and isolated hormone deficiency

Agammaglobulinemia causes undetectable immunoglobulins (antibodies) while hypogammaglobulinemia causes reduced level of all serum immunoglobulins due to a defect in the production of functional B-lymphocytes.

Patients affected with agammaglobulinemia usually present early onset periodic bacterial infections, most commonly, respiratory tract and gastrointestinal tract infections. These infections can be severe, life-threatening bacterial infections such as sepsis, meningitis, pneumonia, empyema. Although most viral infections run a typical course in patients with agammaglobulinemia, enteroviral infections are typically severe and can be life-threatening.

Onset of symptoms is commonly in the first year of life although adult onset presentations have been reported. Most patients will be diagnosed as immunodeficient within the first 5 years of age. However, in some cases, patients won’t be diagnosed till 10 years old or adulthood. Infections caused by H.influenzae and S.pneoumoniae are one of the most frequent episodes seen prior a diagnosis and symptoms may continue after treatment with immunoglobulin replacement therapy. Affected individuals are also susceptible to infections by giardia and mycoplasma.

Approximately 90 – 92% of patients with agammaglobulinemia are expected to have a pathogenic variant(s) in one of the genes on this panel.

Gene % of agammaglobulinemia cases attributed
BLNK <1%
BTK ~85%
CD79A <1%
CD79B <1%
IGLL1 <1%
PIK3R1 <1%

Agammaglobulinemia is most commonly inherited in an X-linked recessive manner, but can also be inherited in an autosomal recessive manner.

The prevalence of X-linked agammaglobulinemia has been estimated to roughly 3 to 6 individuals per 1,000,000 males in all racial and ethnic groups. The prevalence for the autosomal recessive form of agammaglobulinemia has not been established, but is much less frequent than X-linked agammaglobulinemia.

This test may be recommended for patients with:

  • early onset recurrent bacterial infections
  • very low levels of circulating immunoglobulins and B-cells in serum

  1. Plebani, A, et al. Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study. Clin. Immunol. 2002; 104(3):221-30. PMID: 12217331
  2. Conley, ME, Howard, V. Clinical findings leading to the diagnosis of X-linked agammaglobulinemia. J. Pediatr. 2002; 141(4):566-71. PMID: 12378199
  3. Conley, ME, et al. Genetic analysis of patients with defects in early B-cell development. Immunol. Rev. 2005; 203:216-34. PMID: 15661032
  4. Winkelstein, JA, et al. X-linked agammaglobulinemia: report on a United States registry of 201 patients. Medicine (Baltimore). 2006; 85(4):193-202. PMID: 16862044
  5. Conley, ME, et al. A minimally hypomorphic mutation in Btk resulting in reduced B cell numbers but no clinical disease. Clin. Exp. Immunol. 2008; 152(1):39-44. PMID: 18241230
  6. Smith, CIE, Berglöf, A. X-Linked Agammaglobulinemia. 2001 Apr 05. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301626
  7. Bearden, D, et al. Enteroviruses in X-Linked Agammaglobulinemia: Update on Epidemiology and Therapy. J Allergy Clin Immunol Pract. 2016; 4(6):1059-1065. PMID: 26883540
  8. Recher, M, et al. Intronic SH2D1A mutation with impaired SAP expression and agammaglobulinemia. Clin. Immunol. 2013; 146(2):84-9. PMID: 23280491
  9. Hull, S, et al. Expanding the Phenotype of TRNT1-Related Immunodeficiency to Include Childhood Cataract and Inner Retinal Dysfunction. JAMA Ophthalmol. 2016; 134(9):1049-53. PMID: 27389523
  10. Berglöf, A, et al. Agammaglobulinemia: causative mutations and their implications for novel therapies. Expert Rev Clin Immunol. 2013; 9(12):1205-21. PMID: 24215410
  11. Zhang, ZY, et al. Clinical characteristics and molecular analysis of 21 Chinese children with congenital agammaglobulinemia. Scand. J. Immunol. 2010; 72(5):454-9. PMID: 21039741

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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

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
BLNK NM_013314.3
BTK NM_000061.2
CD27 NM_001242.4
CD79A NM_001783.3
CD79B NM_000626.3
CR2 NM_001006658.2
CTLA4 NM_005214.4
DCLRE1C NM_001033855.2
GATA2 NM_032638.4
ICOS NM_012092.3
IGLL1 NM_020070.3
IL21 NM_021803.3
IL21R NM_021798.3
JAK3 NM_000215.3
LRBA NM_006726.4
MOGS NM_006302.2
NFKB2 NM_001077494.3
PIK3CD NM_005026.3
PIK3R1 NM_181523.2
PLCG2 NM_002661.4
PRKCD NM_006254.3
RAC2 NM_002872.4
RAG1 NM_000448.2
SH2D1A NM_002351.4
STAT3 NM_139276.2
STXBP2 NM_006949.3
TNFRSF13B NM_012452.2
TNFRSF13C NM_052945.3
TNFSF12 NM_003809.2
TRNT1 NM_182916.2
XIAP NM_001167.3