Deep Immunogenetics

Mosaic variant detection by deep sequencing of genes associated with immune dysregulation

Somatic mosaic variants have been uncovered as important drivers and modifiers of immune deficiencies and immune dysregulation in the scientific literature of the last years. They may be present in blood with frequencies of only 5 % or even lower, and therefore often escape detection in standard next-generation sequencing panels, exome enrichments, and especially genome enrichments. Our high-coverage enrichment Deep Immunogenetics (DIG) is a diagnostic tool for the targeted identification of somatic mosaic sequence variants in immune disorders.

The Deep Immunogenetics enrichment contains 337 genes, that are covered with approximately 750-1000X reads per base. The high coverage enables a detection limit for mosaic sequence variants of ≥5% of the sequenced reads, and ≥2% for variants in known hotspots. All genes of the enrichment are sequenced in parallel, and the genes associated with the patient’s phenotype are interpreted. Below you will find our pre-designed gene sets as well as a list of all genes of the enrichment.

We offer gene sets for autoimmune-lymphoproliferative and autoinflammatory diseases. It is also possible to compile your own set of genes for individual diagnostic questions after consultation.

Are you insured in Germany? Our colleagues at the Zentrum für Humangenetik Tübingen will gladly support you!

What We Offer with the Panel for Deep Immunogenetics

Updates

The gene selection is regularly adapted to the current scientific knowledge

Variant Detection

Identification of somatic mosaic sequence variants in immune disorders

Comprehensive Medical Report

Including the ACMG criteria used to classify the variants

Highest Quality

All steps are carried out in-house

Our Promise to You

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Fast Turnaround Time

2–4 weeks after sample receipt

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Safety

Highest confidentiality and quality standards

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Reliability

Reliable support throughout all steps

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Comprehensibility

Clearly prepared medical report

Your Benefits

It is possible to request single or multiple predefined gene sets. In addition to the complete analysis of the genes of the requested gene set, we extend the analysis by additional genes for differential diagnosis. We report variants of unknown significance (ACMG class 3) and pathogenic and probably pathogenic variants (ACMG classes 4 and 5) for the primarily ordered gene set. For the genes included due to differential diagnosis, we restrict the reporting to pathogenic and probably pathogenic variants (ACMG classes 4 and 5), which could be related to the indication of the person seeking advice.

Method

The enrichment of the coding regions and the adjacent intronic regions is performed using an in-solution hybridization technology. The selection of the targeted regions and the design of the enrichment baits is performed in-house. High-throughput sequencing is performed on our Illumina platforms. Bioinformatic processing of the data is achieved using an in-house computer cluster.

Following data processing, our team of scientists and specialists in human genetics analyze the data and issue a medical report.

General Information

Material

  • 1-2 ml EDTA blood (recommended sample type) or
  • 1-2 µg genomic DNA
  • Order Form with declaration of consent

Here you can find more information on how to ship your sample safely.

Costs

The prices for our human genetic diagnostics depend on the size of the selected diagnostic panel and the selected gene sets. All prices include sequencing, bioinformatic analysis, and issuing of a medical report by our team of experts in human genetic diagnostics.

Diagnostic Process

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Counseling & Test Selection

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Sampling & Shipment

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Sample Analysis

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Medical Report & Counseling

Gene Sets – Deep Immunogenetics

We recommend the high-coverage Deep Immunogenetics enrichment as a second-tier analysis after exome or panel diagnostics.

Optional Step 1: Exome Enrichment

Abnormal Lymphoproliferation (29 Genes, AID05)

EBV susceptibility with lymphoproliferation / ALPS

CARMIL2, CASP10, CASP8, CD27, CD70, CORO1A, CTPS1, FADD, FAS, FASLG, IL2RA, IL2RB, ITK, KRAS, LAT, LRBA, MAGT1, NFKB1, NRAS, PIK3CD, PIK3R1, PRKCD, RASGRP1, SH2D1A, STAT3, STK4, TET2, TNFRSF9, XIAP

Periodic Fever Syndromes with/without Urticaria (9 Genes, AID01)

ELANE, MEFV, MVK, NLRP12, NLRP3, NOD2, OTULIN, PSTPIP1, TNFRSF1A

Further Autoinflammatory Disorders without Type I
Interferonopathies (35 Genes, AID02)

Incl. inflammation of the skin, joints and bones, vasculitis

ADA2, ADAM17, AP1S3, ARPC1B, CARD11, CARD14, COPA, DPP9, ELF4, HAVCR2, HCK, IL1RN, IL36RN, LPIN2, LYN, NCKAP1L, NFKB1, NLRC4, NLRP1, NOD2, OTULIN, PLCG2, POMP, PSMA3, PSMB10, PSMB4, PSMB8, PSMB9, PSMG2, PSTPIP1, RELA, RIPK1, SLC29A3, SYK, TNFAIP3

Further gene sets can be found on the order forms for immune disorders and blood disorders.

Step 2: Deep Immunogenetics Enrichment

Lymphoproliferation and Autoimmunity (47 Genes, DIG01)

ADA2, CARD11, CARMIL2, CASP10, CASP8, CBLB, CCL22, CD27, CD70, CDC42, CTLA4, CTPS1, DEF6, FADD, FAS, FASLG, HAVCR2, IKZF1, IKZF3, IL2RA, IL2RB, ITK, JAK2, JAK3, KRAS, LAT, LRBA, MAGT1, NCKAP1L, NFKB1, NRAS, PIK3CD, PIK3R1, PRKCD, PTEN, PTPN11, RASGRP1, SH2D1A, SOCS1, STAT1, STAT3, STAT5B, STK4, TET2, TNFRSF9, XIAP, ZAP70

Autoinflammation (60 Genes, DIG02)

ADA2, AP3B1, BACH2, CARD11, CARD14, CDC42, CEBPE, COPA, CTLA4, GATA2, HAVCR2, HCK, IFIH1, IL6ST, JAK1, LYN, LYST, NCKAP1L, NFKB1, NLRC4, NLRP1, NLRP12, NLRP3, NOD2, OAS1, PDGFRA, PDGFRB, PIK3CG, PLCG1, PLCG2, POMP, PRF1, PSMA3, PSMB10, PSMB4, PSMB8, PSMB9, PSMG2, PSTPIP1, RAB27A, RC3H1, RELA, RIPK1, SLC7A7, SOCS1, STAT1, STAT2, STAT4, STAT6, STING1, STX11, STXBP2, SYK, TLR8, TNFAIP3, TNFRSF1A, TREX1, UBA1, UNC13D, XIAP

Gene Directory – Panel for Deep Immunogenetics

ABL1, ACD, ADA, ADA2, AK2, AP3B1, ARID1A, ASXL1, ASXL2, ATM, ATR, ATRX, B2M, BACH2, BCL10, BCL11B, BCL2, BCOR, BCORL1, BIRC3, BLM, BRAF, BRCA1, BRCA2, BRCC3, BRIP1, BTK, CALR, CARD11, CARD14, CARMIL2, CASP10, CASP8, CBL, CBLB, CBLC, CCL22, CCND1, CD247, CD27, CD28, CD3D, CD3E, CD3G, CD48, CD70, CD79B, CD8A, CDC42, CDKN2A, CEBPA, CEBPE, CHD7, CIITA, COPA, COPG1, CREBBP, CSF1R, CSF3R, CSNK1A1, CTC1, CTCF, CTLA4, CTPS1, CUX1, CXCR4, CYBA, CYBB, CYBC1, DCLRE1C, DDX41, DEF6, DIS3, DKC1, DNAJC21, DNMT3A, DOCK2, DUT, EFL1, EGR1, EP300, ERBIN, ERCC4, ERCC6L2, ETNK1, ETV6, EXOC3L2, EZH2, FADD, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FAS, FASLG, FBXW7, FCHO1, FERMT1, FLT3, FOXI3, FOXN1, FOXO1, FYN, G6PD, GATA1, GATA2, GNAS, GNB1, GRHL2, HAVCR2, HCK, HRAS, ICOS, ID3, IDH1, IDH2, IFIH1, IKBKB, IKZF1, IKZF3, IL21R, IL2RA, IL2RB, IL2RG, IL6R, IL6ST, IL7R, IRF4, ITK, JAK1, JAK2, JAK3, KDM6A, KIT, KLF2, KLHL6, KMT2A, KMT2D, KRAS, LAT, LCK, LCP2, LIG1, LIG4, LIPA, LRBA, LYN, LYST, MAD2L2, MAGT1, MALT1, MAP2K1, MAP3K14, MECOM, MEF2B, MPL, MPO, MSN, MTHFD1, MTR, MYC, MYD88, MYSM1, NBN, NCF1, NCF2, NCF4, NCKAP1L, NF1, NFE2L2, NFKB1, NFKB2, NFKBIA, NHEJ1, NHP2, NLRC4, NLRP1, NLRP12, NLRP3, NOD2, NOP10, NOTCH1, NOTCH2, NPM1, NRAS, OAS1, ORAI1, PALB2, PARN, PAX1, PAX5, PDGFRA, PDGFRB, PGM3, PHF6, PIGA, PIK3CD, PIK3CG, PIK3R1, PLCG1, PLCG2, PNP, POMP, POT1, PPM1D, PRF1, PRKCD, PRKDC, PRPF40B, PRPF8, PSMA3, PSMB10, PSMB4, PSMB8, PSMB9, PSMG2, PSTPIP1, PTEN, PTPN11, PTPRC, RAB27A, RAC2, RAD21, RAD51, RAD51C, RAF1, RAG1, RAG2, RASGRP1, RBM8A, RBSN, RC3H1, RECQL4, RELA, RELB, RFWD3, RFX5, RFXANK, RFXAP, RHOA, RIPK1, RMRP, RPL11, RPL15, RPL26, RPL27, RPL31, RPL35A, RPL5, RPS10, RPS15, RPS19, RPS24, RPS26, RPS27, RPS28, RPS29, RPS7, RPSA, RTEL1, RUNX1, SAMD9, SAMD9L, SBDS, SETBP1, SF1, SF3A1, SF3B1, SGK1, SH2B3, SH2D1A, SLC19A2, SLC46A1, SLC7A7, SLX4, SMC1A, SMC3, SOCS1, SRP54, SRP72, SRSF2, STAG2,STAT1, STAT2, STAT3, STAT4, STAT5B, STAT6, STIM1, STING1, STK4, STX11, STXBP2, SUZ12, SYK, TAP1, TAP2, TAPBP, TBX1, TCN2, TERC, TERT, TET2, TFRC, THPO, TINF2, TLR8, TNFAIP3, TNFRSF1A, TNFRSF9, TP53, TREX1, TSR2, U2AF1, U2AF2, UBA1, UBE2T, UBR5, UNC13D, USB1, VAV1, WAS, WIPF1, WRAP53, WT1, XIAP, XPO1, XRCC2, ZAP70, ZCCHC8, ZEB2, ZRSR2

The Deep Immunogenetics enrichment comprises 337 genes. Please contact us if you are interested in an individual selection of the genes listed.

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Diagnostic Support

We will assist you in selecting the diagnostic strategy – for each patient.

Keimbahn Team der CeGaT