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  • Test code: 08138
  • 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 Syndromic Combined Immunodeficiency (CID) Panel

Test description

The Invitae Syndromic Combined Immunodeficiency (CID) Panel analyzes 37 genes that are associated with syndromic combined immunodeficiency (CID) diseases. The syndromic CID have additional non-immunologic symptoms in addition to immunodeficiency. 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 (40 genes)

ACD ACD ATM CHD7 CTC1 DCLRE1B DKC1 DNMT3B EPG5 FOXN1 NBN NFKBIA NHP2 NOP10 ORAI1 PARN PARN PGM3 PMS2 PNP POLE RMRP RTEL1 RTEL1 SEMA3E SMARCAL1 SP110 SPINK5 STAT3 STAT5B STIM1 TBX1 TCN2 TERC TERT TINF2 TTC7A WAS WIPF1 ZBTB24

Syndromic combined immunodeficiency (CID) including:




Gene Disorder Protein name Protein symbol
ACD DKC due to TPP1 deficiency telomere protein TPP1 TPP1
ATM Ataxia-telangiectasia ataxia-telangiectasia mutated ATM
CHD7 CHARGE syndrome chromodomain helicase DNA-binding protein 7 CHD7
CTC1 DKC conserved telomere maintenance component 1 CTC1
DCLRE1B DKC due to DCLRE1B deficiency Apollo SNM1; apollo
DKC1 DKC due to Dyskerin deficiency dyskerin DKC1
DNMT3B Immunodeficiency with centromeric instability and facial anomalies (ICF1) DNA methyltransferase 3B DNMT3B
EPG5 Vici syndrome due to EPG5 deficiency ectopic P-granules autophagy protein 5 EPG5
FOXN1 Winged helix deficiency (nude) AAB: syndromic SCID forkhead box N1 transcription factor FOXN1; nude
NBN Nijmegen breakage syndrome nibrin NIBRIN
NFKBIA EDA-ID IKBA gain I-kappa-B-alpha IKBA
NHP2 DKC due to nucleolar protein family A member 2 (NHP2) deficiency nucleolar protein family A member 2 NOLA2
NOP10 DKC due to nucleolar protein family A member 3 (NHP3) or NOP10 deficiency nucleolar protein family A member 3 NOLA3
ORAI1 ORAI-I deficiency calcium release-activated calcium modulator 1 ORAI1
PARN DKC due to PARN deficiency polyadenylate-specific ribonuclease PARN
PGM3 PGM3 deficiency phosphoglucomutase 3 PGM3
PMS2 PMS2 deficiency PMS2
PNP Purine nucleoside phosphorylase (PNP) deficiency purine nucleoside phosphorylase PNP
POLE Facial dysmorphism, immunodeficiency, livedo, and short stature (FILS) syndrome DNA polymerase epsilon POLE
RMRP Cartilage hair hypoplasia Mitochondrial RNA-processing endoribonuclease (RNase MRP) RNA RNase MRP (RNA)
RTEL1 DKC due to regulator of telomere elongation (RTEL1) deficiency regulator of telomere elongation helicase 1 RTEL1
SEMA3E CHARGE syndrome semaphorin 3E SEMA3E
SMARCAL1 Schimke Immunoosseous Dysplasia SMARCA like protein 1 SMARCAL1
SP110 Hepatic veno-occlusive disease with immunodeficiency speckled 110 kDa SP110
SPINK5 Comel-Netherton syndrome lymphoepithelial kazal type related inhibitor LEKT1
STAT3 AD-HIES (Job or Buckley Syndrome), STAT3 GOF mutations signal transducer and activator of transcription 3 STAT3
STAT5B STAT5b deficiency signal transducer and activator of transcription 5b STAT5B
STIM1 STIM1 deficiency stromal interaction molecule 1 STIM1
TBX1 DiGeorge T-box 1 TBX1
TCN2 Transcobalamin 2 deficiency transcobalamin 2 TCN2
TERC DKC telomerase RNA component TERC
TERT DKC due to TERT deficiency telomerase reverse transcriptase TERT
TINF2 DKC due to TINF2 deficiency telomerase interacting factor 2 TINF2
TTC7A Immunodeficiency with multiple intestinal atresias tetratricopeptide repeat (TPR) domain containing protein 7A TTC7A
WAS Wiskott-Aldrich syndrome, X-linked neutropenia/ myelodysplasia WAS protein WASP
WIPF1 WIP deficiency WASP-interacting protein WIP
ZBTB24 Immunodeficiency with centromeric instability and facial anomalies (ICF2) zinc finger and BTB-domain containing protein 24 ZBTB24

The syndromic combined immunodeficiencies (CID) are a group of disorders that have non-immunologic symptoms in addition to immunodeficiency. These additional symptoms may or may not present in the newborn period or may be difficult to diagnose. Syndromic features may include intellectual disability, short stature, mild dysmorphism, alopecia, ataxia, skin and nail abnormalities, microcephaly, congenital heart malformations, and others. Patients can have variable immunodeficiency from mild to as severe as SCID.

CIDs can be inherited in several patterns, including autosomal dominant, autosomal recessive, and X-linked.

The prevalence of syndromic CID is not well-established, but reports may be underestimated due to the broad spectrum of phenotypes associated with these conditions.

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
ACD NM_001082486.1
ACD NM_001082486.1
ATM NM_000051.3
CHD7 NM_017780.3
CTC1 NM_025099.5
DCLRE1B NM_022836.3
DKC1 NM_001363.4
DNMT3B NM_006892.3
EPG5 NM_020964.2
FOXN1 NM_003593.2
NBN NM_002485.4
NFKBIA NM_020529.2
NHP2 NM_017838.3
NOP10 NM_018648.3
ORAI1 NM_032790.3
PARN NM_002582.3
PARN NM_002582.3
PGM3 NM_001199917.1
PMS2 NM_000535.5
PNP NM_000270.3
POLE NM_006231.3
RMRP NR_003051.3
RTEL1 NM_001283009.1
RTEL1 NM_001283009.1
SEMA3E NM_012431.2
SMARCAL1 NM_014140.3
SP110 NM_004509.3
SPINK5 NM_006846.3
STAT3 NM_139276.2
STAT5B NM_012448.3
STIM1 NM_003156.3
TBX1 NM_080647.1
TCN2 NM_000355.3
TERC NR_001566.1
TERT NM_198253.2
TINF2 NM_001099274.1
TTC7A NM_020458.3
WAS NM_000377.2
WIPF1 NM_001077269.1
ZBTB24 NM_014797.2