• Test code: 08131
  • 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

Invitae T-B-NK- Severe Combined Immunodeficiency (SCID) Panel

Test description

The Invitae T-B-NK- Severe Combined Immunodeficiency (SCID) Panel analyzes 2 genes that are associated with severe combined immune deficiency which typically present with a lymphocyte profile of T-B-NK-. Although the lymphocyte profile observed in patients with pathogenic variants in ADA and AK2 are both T/B/NK deficient, the clinical presentations are distinct.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of disease-causing variants provide accurate risk assessment and carrier status for at-risk relatives.

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Primary panel (2 genes)

T-cell negative, B-cell negative, NK-cell negative severe combined immunodeficiency (SCID) including:

Gene Disorder Protein name Protein symbol
ADA Adenosine deaminase (ADA) deficiency adenosine deaminase ADA
AK2 Reticular dysgenesis, AK2 deficiency adenylate kinase-2 AK2

ADA-related SCID is characterized by infantile, childhood or adult onset recurrent, overwhelming viral, bacterial and fungal infections and failure to thrive. ADA-related SCID can have variable age of onset and variable clinical severity. Greatly reduced adenosine deaminase activity leading to intracellular accumulation of adenosine and deoxyadenosine is diagnostic for ADA-related SCID.

Reticular dysgenesis is a rare form of severe combined immunodeficiency (SCID) characterized by neonatal onset of recurrent/opportunistic bacterial and fungal infections, congenital agranulocytosis, severe leukopenia, hypoplasia or aplasia of the thymus and lymphoid tissues, and absent hematopoietic elements within the bone marrow. Death typically occurs within the first few weeks of life.

In individuals with a confirmed enzymatic diagnosis of ADA deficiency, greater than 90% of individuals will have homozygous or compound heterozygous pathogenic variants identified in the ADA gene (PMID: 11037300).

AK2 is the only gene known to be associated with reticular dysgenesis. However, due to the rarity of this condition, the percent of T-B-NK- SCID attributed to pathogenic variants in AK2 is currently unknown.

Adenosine deaminase deficiency and reticular dysgenesis are both inherited in an autosomal recessive pattern.

T-B-NK- SCID accounts for approximately 10% of all cases of SCID.The incidence of adenosine deaminase deficiency is approximately 1:200,000 live births. The prevalence of reticular dysgenesis is currently unknown.

Testing for the T-B-NK- SCID panel may be considered in individuals with:

  • low T-cell receptor excision circles (TRECs) on newborn screening
  • less than 1% ADA enzymatic activity in red cells
  • recurrent opportunistic infections with marked lymphocytopenia
  • marked decrease in thymic function
  • absent thymic shadow on chest radiogram
  • failure to thrive (FTT)
  • chronic diarrhea
  • skeletal abnormalities including scapular spurring and anterior rib cupping
  • absent granulocytes and lymphocytes in peripheral blood
  • fatal septicemia within days after birth
  • family history of SCID

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
ADA NM_000022.2
AK2 NM_001625.3