Early Onset IBD Gene Panel - Clinical Genetic Test - GTR

Genetic Testing Registry

View Advanced Search Options

Classic view of this page

Early Onset IBD Gene Panel

Clinical Genetic Test

offered by

Mayo Clinic Laboratories

View lab's test page

GTR Test Accession: GTR000611987.2

INHERITED DISEASEIMMUNOLOGYSYNDROMIC DISEASE ... View more

Last updated in GTR: 2024-05-17

Last annual review date for the lab: 2024-05-28

At a Glance

Test purpose:

Diagnosis; Predictive; Therapeutic management

Conditions (163):

Inflammatory bowel disease; Activated PI3K-delta syndrome; Acute febrile neutrophilic dermatosis more...

Genes (110):

ADA (20q13.12); ADAM17 (2p25.1); AICDA (12p13.31); AIRE (21q22.3); ALPI (2q37.1) more...

Methods (1):

Molecular Genetics - Sequence analysis of the entire coding region: Next-Generation (NGS)/Massively parallel sequencing (MPS)

Target population:

Providing a comprehensive genetic evaluation for patients with a personal …

Clinical validity:

Not provided

Clinical utility:

Establish or confirm diagnosis; Guidance for management

Ordering Information

Offered by:

Mayo Clinic Laboratories
View lab's website
View lab's test page

Test short name:

EOIBD

Specimen Source:

Fibroblasts
Peripheral (whole) blood
Skin
View specimen requirements

Who can order:

Genetic Counselor
Health Care Provider
Licensed Dentist
Licensed Physician
Nurse Practitioner
Physician Assistant
Public Health Mandate
Registered Nurse

Test Order Code:

EOIBD
View other test codes

LOINC codes:

**LOINC codes notice

CPT codes:

81443

**AMA CPT codes notice

Lab contact:

Elyse Love, MS, CGC, Certified Genetic counselor, CGC, Genetic Counselor
[email protected]
1-800-533-1710

Contact Policy:

Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.

How to Order:

https://www.mayocliniclabs.com/test-catalog/Overview/620120#Specimen
Order URL

Test development:

Test developed by laboratory (no manufacturer test name)

Informed consent required:

Based on applicable state law

Pre-test genetic counseling required:

Decline to answer

Post-test genetic counseling required:

Decline to answer

Recommended fields not provided:

Test strategy

Conditions

Total conditions: 163

Condition/Phenotype	Identifier

Test Targets

Genes

Total genes: 110

Gene	Associated Condition	Germline or Somatic	Allele (Lab-provided)	Variant in NCBI

Methodology

Total methods: 1

Method Category

Test method

Instrument

Sequence analysis of the entire coding region

Next-Generation (NGS)/Massively parallel sequencing (MPS)

Illumina NovaSeq 6000

Clinical Information

Test purpose:

Diagnosis; Predictive; Therapeutic management

Clinical utility:

Establish or confirm diagnosis

View citations (1)

https://www.mayocliniclabs.com/test-catalog/Overview/620120#Clinical-and-Interpretive

Guidance for management

View citations (1)

https://www.mayocliniclabs.com/test-catalog/Overview/620120#Clinical-and-Interpretive

Target population:

Providing a comprehensive genetic evaluation for patients with a personal or family history suggestive of an inherited inflammatory bowel disorder. Establishing a diagnosis of a monogenic early onset inflammatory bowel disease, allowing for appropriate management and surveillance for disease features based on the gene and/or variant involved. Identifying variants within … View more

View citations (5)

Uhlig HH, Schwerd T, Koletzko S, Shah N, Kammermeier J, Elkadri A, Ouahed J, Wilson DC, Travis SP, Turner D, Klein C, Snapper SB, Muise AM, . The diagnostic approach to monogenic very early onset inflammatory bowel disease. Gastroenterology. 2014;147(5):990-1007.e3. doi:10.1053/j.gastro.2014.07.023. Epub 2014 Jul 21. PMID: 25058236.
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, . Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-24. doi:10.1038/gim.2015.30. Epub 2015 Mar 05. PMID: 25741868.
Maintaining intestinal health: the genetics and immunology of very early onset inflammatory bowel disease. Kelsen JR, et al. Cell Mol Gastroenterol Hepatol. 2015;1(5):462-476. doi:10.1016/j.jcmgh.2015.06.010. PMID: 26393237.
From Genes to Mechanisms: The Expanding Spectrum of Monogenic Disorders Associated with Inflammatory Bowel Disease. Uhlig HH, et al. Inflamm Bowel Dis. 2016;22(1):202-12. doi:10.1097/MIB.0000000000000614. PMID: 26512716.
Very Early Onset Inflammatory Bowel Disease: A Clinical Approach With a Focus on the Role of Genetics and Underlying Immune Deficiencies. Ouahed J, et al. Inflamm Bowel Dis. 2020;26(6):820-842. doi:10.1093/ibd/izz259. PMID: 31833544.

Variant Interpretation:

What is the protocol for interpreting a variation as a VUS?
All detected variants are evaluated according to the most recent American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) recommendations. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Are family members with defined clinical status recruited to assess significance of VUS without charge?
Contact lab for details

Will the lab re-contact the ordering physician if variant interpretation changes?
Not provided. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

Research:

Is research allowed on the sample after clinical testing is complete?
Research testing is only performed under IRB approved protocol with an opt-out policy in place.

Recommended fields not provided:

Clinical validity, Are family members with defined clinical status recruited to assess significance of VUS without charge?, Will the lab re-contact the ordering physician if variant interpretation changes?, Sample negative report, Sample positive report

Technical Information

Test Procedure:

Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least … Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletions/insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed. There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. See Targeted Genes and Methodology Details for Early Onset Monogenic Inflammatory Bowel Disease (IBD) Gene Panel for details regarding the targeted gene regions identified by this test.(Unpublished Mayo method) (Unpublished Mayo method) Genes analyzed: ADA, ADAM17, AICDA, AIRE, ALPI, ANKZF1, ARPC1B, ASAH1, BACH2, BTK, CARMIL2, CASP8, CD3G, CD40LG, CD55, COL7A1, CTLA4, CYBA, CYBB, CYBC1, DCLRE1C, DEF6, DGAT1, DKC1, DOCK8, DUOX2, EPCAM, FCHO1, FERMT1, FOXP3, G6PC(G6PC1), G6PC3, GUCY2C, HPS1, HPS3, HPS4, HPS6, ICOS, IFIH1, IKBKG, IL10, IL10RA, IL10RB, IL21, IL21R, IL2RA, IL2RB, IL2RG, IL7R, ITCH, ITGB2, JAK1, LCT, LIG4, LRBA, MALT1, MEFV, MVK, MYO5B, NCF2, NCF4, NEUROG3, NFKBIA, NLRC4, PAX1, PCSK1, PIK3CD, PIK3R1, PLCG2, PLVAP, POLA1, RAG1, RAG2, RIPK1, RTEL1, SH2D1A, SI, SKIV2L, SLC10A2, SLC26A3, SLC37A4, SLC39A4, SLC51B, SLC5A1, SLC9A3, SPINT2, STAT1, STAT3, STAT5B, STIM1, STX3, STXBP2, TGFB1, TGFBR1, TGFBR2, TLR3, TNFAIP3, TRIM22, TRNT1, TTC37, TTC7A, UNC45A, WAS, WIPF1, XIAP, ZAP70, and ZBTB24 View more

Availability:

Tests performed
Entire test performed in-house

Analytical Validity:

At least 99% of the bases are covered at a read depth >30X. Sensitivity is estimated at >99% for single nucleotide variants, >94% for indels up to 39 base pairs, >95% for deletions up to 75 base pairs and insertions up to 47 base pairs.

Assay limitations:

Clinical Correlations: Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete. If testing was performed because of a clinically significant family history, it is often useful to first test … Clinical Correlations: Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete. If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals. To discuss the availability of additional testing options or for assistance in the interpretation of these results, contact Mayo Clinic Laboratories genetic counselors at 800-533-1710. Technical Limitations: Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered. There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria. This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Deletions-insertions (delins) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller delins. Deletion/Duplication Analysis: This analysis targets single and multi-exon deletions/duplications; however, in some instances, single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected. This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results. Genes may be added or removed based on updated clinical relevance. For detailed information regarding gene specific performance and technical limitations, see Method Description or contact a laboratory genetic counselor. If the patient has had an allogeneic hematopoietic stem cell transplant or a nonleukoreduced blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant. Reclassification of Variants: Currently, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages health care providers to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time. Due to broadening genetic knowledge, it is possible that the laboratory may discover new information of relevance to the patient. Should that occur, the laboratory may issue an amended report. Variant Evaluation: Evaluation and categorization of variants are performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline. (1) Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported. Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgement. Rarely, incidental or secondary findings may implicate another predisposition or presence of active disease. These findings will be carefully reviewed to determine whether they will be reported. View more

Proficiency testing (PT):

Is proficiency testing performed for this test?
Yes

Method used for proficiency testing:
Platform PT performed

Description of internal test validation method: Help
This test was laboratory developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements

VUS:

Software used to interpret novel variations
Variants may be analyzed using any combination of the following: Alamut, REVEL, Polyphen-2, SIFT, AGVGD, MutationTaster, SpliceSiteFinder-like, MaxEntScan, NNSPLICE, GeneSplicer, SpliceAI, gene-specific online databases, ISCA, UCSC Genome Browser

Laboratory's policy on reporting novel variations
All novel alterations and copy number variants are evaluated for potential pathogenicity and included in the written report, accordingly.

Recommended fields not provided:

Test Confirmation, Citations to support assay limitations, Citations to support internal test validation method, Citations for Analytical validity, PT Provider, Description of PT method, Major CAP category, CAP category, CAP test list

Regulatory Approval

FDA Review:

Category: FDA exercises enforcement discretion

Additional Information

Reviews:

PubMed Clinical Queries

Clinical resources:

Practice guidelines:

Consumer resources:

IMPORTANT NOTE: NIH does not independently verify information submitted to GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.