Agammaglobulinemia Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
2691 BLNK 81479,81479 Order Options and Pricing
BTK 81406,81479
CD79A 81479,81479
CD79B 81479,81479
IGHM 81479,81479
IGLL1 81479,81479
LRRC8A 81479,81479
PIK3CD 81479,81479
PIK3R1 81479,81479
SH2D1A 81404,81403
SLC39A7 81479,81479
TCF3 81479,81479
TOP2B 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
2691Genes x (13)81479 81403, 81404, 81406, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

Agammaglobulinemia is an immunodeficiency due to defects in B-cell maturation. While the exact incidence of agammaglobulinemia is unknown, a study of the United States registry of patients with X-linked agammaglobulinemia estimates the incidence to be ~1 in 380,000 live births (~1 in 200,000 male births) (Winkelstein et al. 2006. PubMed ID: 16862044). Patients with agammaglobulinemia present with recurrent bacterial infections including Haemophilus influenza, Strephtococcus pneumoniae, and staphylococci due to loss of antibody mediated immune responses. Common sites of infection include skin, respiratory tract, gastrointestinal tract, and joints. Severe infections can be life threatening due to empyema, meningitis, and sepsis. Infections typically occur after the first few months of life as maternal immunoglobulins are protective (Conley and Howard. 2011. PubMed ID: 20301626). Symptoms primarily occur in the first two years of life although ~10% of cases have delayed onset with immunodeficiency not being apparent until after ten years of age. Bimonthly gammaglobulin transfusions are the mainstay treatment with affected individuals receiving heightened antibiotic regimen to ward off pathogens during infection (Quartier et al. 1999. PubMed ID: 10228295).

Genetic testing is helpful in the differential diagnosis of agammaglobulinemia from other immunodeficiency syndromes such as common variable immunodeficiency and Omenn syndrome, infectious diseases, malignancies, and drug induced agammaglobulinemia (Conley and Howard. 2011. PubMed ID: 20301626; Conley et al. 1999. PubMed ID: 10600329).

Genetics

This test includes genes identified through literature, OMIM, and HGMD searches that have a reported association with a severe reduction in all serum immunoglobulin isotypes with profoundly decreased or absent B cells (agammaglobulinemia) (Bousfiha et al. 2018. PubMed ID: 29226301; Picard et al. 2018. PubMed ID: 29226302; Tangye et al. 2020. PubMed ID: 31953710).

Primary agammaglobulinemia is most commonly inherited as an X-linked trait. X-linked agammaglobulinemia (XLA) represents about 85-95% cases of agammaglobulinemia via pathogenic variants in the BTK gene. Variants in BTK may be inherited with ~40% of XLA cases having a previously affected family member, or they may occur de novo (Winkelstein et al. 2006. PubMed ID: 16862044). There is one report of a heterozygous female with XLA, however, the majority of female carriers are asymptomatic (Takada et al. 2004. PubMed ID: 12958074). While the disease is fully penetrant, no clear genotype-phenotype correlation has been established (Väliaho et al. 2006. PubMed ID: 16969761; Holinski-Feder et al. 1998. PubMed ID: 9445504). To date, over 700 different pathogenic variants in the BTK gene have been reported with no single variant representing more than 3% of XLA cases (Conley et al. 2005. PubMed ID: 15661032; Lindvall et al. 2005. PubMed ID: 15661031; Väliaho et al. 2006. PubMed ID: 16969761). Causative variants may include missense, nonsense, splicing, regulatory, or copy number alterations. Large deletions, duplications, and rearrangements are present in less than 8% of XLA cases (Conley and Howard. 2011. PubMed ID: 20301626; Conley et al. 1998. PubMed ID: 9545398; Kanegane et al. 2001. PubMed ID: 11742281).

Autosomal recessive and autosomal dominant forms of agammaglobulinemia have also been documented. Autosomal recessive forms of the disease are due to pathogenic variants in the BLNK, CD79A, CD79B, IGHM, IGLL1, PIK3CD, PIK3R1, SH2D1A, and SLC39A7 genes. Autosomal dominant forms of the disease have been associated with pathogenic variants in the LRRC8A and TOP2B genes. Agammaglobulinemia via pathogenic variants in the TCF3 gene may be inherited in an autosomal recessive or autosomal dominant manner. In addition, variants in these genes may arise de novo. Causative variants may include missense, nonsense, splicing, regulatory, or copy number alterations. Autosomal recessive forms of agammaglobulinemia represent ~10% of cases and autosomal dominant forms of disease are less commonly reported.

The majority of products of the genes in this panel are involved in the development, maturation, and function of immune cells, specifically of B cells. In addition, the products of genes in this panel are involved in DNA regulation during transcription and in zinc transportation.

See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

X-linked agammaglobulinemia (XLA) accounts for ~85-95% of cases of agammaglobulinemia in males through pathogenic variants in the BTK gene. Large deletions, duplications, and rearrangements are present in less than 8% of XLA cases (Conley and Howard. 2011. PubMed ID: 20301626; Conley et al. 1998. PubMed ID: 9545398; Kanegane et al. 2001. PubMed ID: 11742281).

Autosomal recessive and autosomal dominant forms of agammaglobulinemia through pathogenic variants in either the BLNK, CD79A, CD79B, IGHM, IGLL1LRRC8A, PIK3CDPIK3R1SH2D1A, SLC39A7TCF3, and TOP2B genes represent ~10% of cases in males. The clinical sensitivity of this specific grouping of genes is difficult to estimate. However, in a study of 12 families with IGHM deficiency, gross deletions were detected in four cases (Lopez Granados et al. 2020. PubMed ID: 12370281). Another study determined that ~60% of X-linked lymphoproliferative disease cases are attributed to pathogenic variants in the SH2D1A gene. Large deletions account for ~25% of all reported SH2D1A pathogenic variants (Sumegi et al. 2000. PubMed ID: 11049992). 

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides full coverage of all coding exons of the genes 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 coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates include individuals with laboratory findings suggestive of agammaglobulinemia, including deficient antibody responses to immunizations, reduced or absent B cell levels, or low serum immunoglobulin levels (below 100 mg/dL). Candidates also include those with a family history of X-linked agammaglobulinemia (XLA) or autosomal recessive or dominant forms of agammaglobulinemia. Molecular testing for the BTK gene specifically is helpful in determining female carrier status of XLA.

Genes

Official Gene Symbol OMIM ID
BLNK 604515
BTK 300300
CD79A 112205
CD79B 147245
IGHM 147020
IGLL1 146770
LRRC8A 608360
PIK3CD 602839
PIK3R1 171833
SH2D1A 300490
SLC39A7 601416
TCF3 147141
TOP2B 126431
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Bousfiha et al. 2018. PubMed ID: 29226301
  • Conley and Howard. 2011. PubMed ID: 20301626
  • Conley et al. 1998. PubMed ID: 9545398
  • Conley et al. 1999. PubMed ID: 10600329
  • Conley et al. 2005. PubMed ID: 15661032
  • Holinski-Feder et al. 1998. PubMed ID: 9445504
  • Kanegane et al. 2001. PubMed ID: 11742281
  • Lindvall et al. 2005. PubMed ID: 15661031
  • Lopez Granados et al. 2020. PubMed ID: 12370281
  • Picard et al. 2018. PubMed ID: 29226302
  • Quartier et al. 1999. PubMed ID: 10228295
  • Sumegi et al. 2000. PubMed ID: 11049992
  • Takada et al. 2004. PubMed ID: 12958074
  • Tangye et al. 2020. PubMed ID: 31953710
  • Väliaho et al. 2006. PubMed ID: 16969761
  • Winkelstein et al. 2006. PubMed ID: 16862044

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.

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


Specimen Types

Specimen Requirements and Shipping Details

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

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.

Total Price: $
×
Copy Text to Clipboard
×