Severe Combined Immunodeficiency (SCID) Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
5209 ADA 81479,81479 Order Options
AK2 81479,81479
CD247 81479,81479
CD3D 81479,81479
CD3E 81479,81479
CORO1A 81479,81479
DCLRE1C 81479,81479
IL2RG 81405,81479
IL7R 81479,81479
JAK3 81479,81479
LAT 81479,81479
LIG4 81479,81479
NHEJ1 81479,81479
PRKDC 81479,81479
PTPRC 81479,81479
RAG1 81479,81479
RAG2 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
5209 Genes x (17) 81479 81405, 81479 $890 Order Options

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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Severe combined immunodeficiency (SCID) encompasses a diverse group of rare, life-threatening disorders. While the true incidence of SCID is unknown, newborn screening studies suggest that 1 in 70,000 births are affected with a range of 1 in 40,000 to 100,000 (Fischer. 2000. PubMed ID: 11091267; Kwan et al. 2014. PubMed ID: 25138334; Kumrah et al. 2020. PubMed ID: 32181275). SCID is caused by genetic defects that inhibit lymphocyte development and function, resulting in no T cell differentiation and abnormal development of B and natural killer (NK) lymphocytes (Fischer. 2000. PubMed ID: 11091267; Kumrah et al. 2020. PubMed ID: 32181275). The broad classification of SCID may be subdivided based on B cell status and further subdivided based on NK cell status, which may provide insight into the causative genetic defect (Kumrah et al. 2020. PubMed ID: 32181275). The clinical features associated with SCID include recurrent and severe bacterial, viral, and fungal infections that begin in infancy (Fischer. 2000. PubMed ID: 11091267; Kwan et al. 2014. PubMed ID: 25138334; Kumrah et al. 2020. PubMed ID: 32181275). Diagnoses are typically made via utilization of flow cytometry-based testing and newborn screening (NBS) assessment of T cell receptor excision circles (TRECs), however it is necessary to establish a genetic diagnosis for genetic counseling, prognostication, and optimization of treatment (Kwan et al. 2014. PubMed ID: 25138334; Kumrah et al. 2020. PubMed ID: 32181275). Prior to NBS, population-based screening was the only method to identify those at risk for SCID prior to the onset of symptoms, however >80% of cases lack a positive family history (Chan and Puck. 2005. PubMed ID: 15696101; Chan et al. 2011. PubMed ID: 21035402; Kwan et al. 2014. PubMed ID: 25138334). The recurrence risk and prognosis may vary depending on the underlying genetics cause of the deficiency. In general, the prognosis is poor if there is a delay is diagnosis and therapy. Early hematopoietic stem cell transplantation (HSCT) is the most established treatment for patients with SCID (Kwan et al. 2014. PubMed ID: 25138334).

Genetics

The four main categories of SCID, based upon which immune cells are defective (T, B, and/or NK cells), each have distinct genetic causes. This panel focuses on genetic causes of T cell negative SCID that have been identified through literature, OMIM, and HGMD searches.

To date, there are 17 genes in which pathogenic variants have been described as causative for T cell negative SCID (Bousfiha et al. 2018. PubMed ID: 29226301; Picard et al. 2018. PubMed ID: 29226302; Tangye et al. 2020. PubMed ID: 31953710). The pattern of inheritance for SCID may be X-linked or autosomal recessive. X-linked SCID caused by IL2RG pathogenic variants accounts for ~40-60% of all cases of SCID (Allenspach et al. 1993. PubMed ID: 20301584; Fischer. 2000. PubMed ID: 11091267; Chan et al. 2011. PubMed ID: 21035402). All other genes in this panel show autosomal recessive inheritance. Adenosine deaminase deficiency due to variants in ADA contributes to ~15-20% of SCID cases (Allenspach et al. 1993. PubMed ID: 20301584; Kalman et al. 2004. PubMed ID: 14726805). Variants in IL7R make up ~5-10% of all SCID cases (Allenspach et al. 1993. PubMed ID: 20301584; Kalman et al. 2004. PubMed ID: 14726805; Chan et al. 2011. PubMed ID: 21035402). Pathogenic variants in AK2, CD247, CD3D, CD3E, CORO1A, DCLRE1C (ARTEMIS), IL2RG, JAK3, LAT, LIG4, NHEJ1, PRKDC, PTPRC, RAG1, and RAG2 together are responsible for ~10% of SCID (Allenspach et al. 1993. PubMed ID: 20301584; Kalman et al. 2004. PubMed ID: 14726805; Chan et al. 2011. PubMed ID: 21035402). Anywhere from ~13-31% of cases of SCID are idiopathic (Chan et al. 2011. PubMed ID: 21035402; Kwan et al. 2014. PubMed ID: 25138334).

Reported pathogenic variants in the causative genes include missense, nonsense, frameshift, splice site, and hypomorphic variants. Large copy number events have also been reported in the causative genes for T cell negative SCID. The frequency of the specific variants is dependent on the underlying genetic cause of disease. Pathogenic variants may be inherited or de novo. Of note, a founder variant in DCLRE1C [c.597C>A (p.Tyr199*)] has been identified in the Navajo Native American population (Li et al. 2002. PubMed ID: 12055248; Kwan et al. 2014. PubMed ID: 25138334). De novo variants may occur in ~50% of cases of X-linked SCID due to IL2RG pathogenic variants (Allenspach et al. 1993. PubMed ID: 20301584). Germline mosaicism has also been reported in cases of X-linked SCID among the Navajo Native American population (O'Marcaigh et al. 1997. PubMed ID: 9049783).

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

Testing Strategy

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

This panel provides 100% 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 reads.

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

Clinical Sensitivity - Sequencing with CNV PGxome

This test covers the common genetic causes of T cell negative SCID (Bousfiha et al. 2018. PubMed ID: 29226301; Picard et al. 2018. PubMed ID: 29226302; Tangye et al. 2020. PubMed ID: 31953710). The clinical sensitivity may vary depending on the B and NK cell status of the patient. While the exact clinical sensitivity of this grouping of genes is difficult to estimate, previous studies suggest that 58-87% of individuals with characteristic features of T cell negative SCID are expected to have a pathogenic variant identified in one of the genes on this panel (Lindegren et al. 2004. PubMed ID: 14724556; Sarzotti-Kelsoe et al. 2009. PubMed ID: 19433858; Chan et al. 2011. PubMed ID: 21035402; Kwan et al. 2014. PubMed ID: 25138334).

Indications for Test

Candidates for testing include those with severe T cell lymphopenia and a lack of adaptive immunity. Testing is especially recommended for newborns identified via newborn screening for SCID using T-cell receptor excision circles (TRECs) screening (Kwan et al. 2014. PubMed ID: 25138334).

Genes

Official Gene Symbol OMIM ID
ADA 608958
AK2 103020
CD247 186780
CD3D 186790
CD3E 186830
CORO1A 605000
DCLRE1C 605988
IL2RG 308380
IL7R 146661
JAK3 600173
LAT 602354
LIG4 601837
NHEJ1 611290
PRKDC 600899
PTPRC 151460
RAG1 179615
RAG2 179616
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®
Primary Antibody Deficiency Panel

Citations

  • Allenspach et al. 1993. PubMed ID: 20301584
  • Bousfiha et al. 2018. PubMed ID: 29226301
  • Chan and Puck. 2005. PubMed ID: 15696101
  • Chan et al. 2011. PubMed ID: 21035402
  • Fischer. 2000. PubMed ID: 11091267
  • Kalman et al. 2004. PubMed ID: 14726805
  • Kumrah et al. 2020. PubMed ID: 32181275
  • Kwan et al. 2014. PubMed ID: 25138334
  • Li et al. 2002. PubMed ID: 12055248
  • Lindegren et al. 2004. PubMed ID: 14724556
  • O'Marcaigh et al. 1997. PubMed ID: 9049783
  • Picard et al. 2018. PubMed ID: 29226302
  • Sarzotti-Kelsoe et al. 2009. PubMed ID: 19433858
  • Tangye et al. 2020. PubMed ID: 31953710

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

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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.

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