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Haploinsufficiency of A20
Clinical Genetic Test
Help
offered by
Inflammatory Disease Section/Clinical Genetics Service
GTR Test Accession: Help GTR000607949.3
INHERITED DISEASECONNECTIVE TISSUESYNDROMIC DISEASE ... View more
Last updated in GTR: 2024-07-08
View version history
Last annual review date for the lab: 2024-07-12 LinkOut
At a Glance
Test purpose: Help
Diagnosis; Mutation Confirmation; Therapeutic management
Conditions (1): Help
Autoinflammatory syndrome, familial, Behcet-like 1
Genes (1): Help
TNFAIP3 (6q23.3)
Methods (1): Help
Molecular Genetics - Mutation scanning of the entire coding region: Bi-directional Sanger Sequence Analysis
Target population: Help
Patients with the haploinsufficiency of A20 (HA20) have been reported …
Clinical validity: Help
The clinical validity of the test is high; there is …
Clinical utility: Help
Establish or confirm diagnosis; Guidance for management
Ordering Information
Offered by: Help
Inflammatory Disease Section/Clinical Genetics Service
Test short name: Help
HA20
Specimen Source: Help
  • Buccal swab
  • Isolated DNA
  • Peripheral (whole) blood
Who can order: Help
  • Genetic Counselor
  • Health Care Provider
  • Licensed Physician
  • Nurse Practitioner
Contact Policy: Help
Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.
Post-test email/phone consultation regarding genetic test results and interpretation is provided to patients/families.
Test service: Help
Clinical Testing/Confirmation of Mutations Identified Previously
Confirmation of research findings
Test development: Help
Test developed by laboratory but exempt from FDA oversight (eg. NYS CLEP approved, offered within a hospital or clinic)
Informed consent required: Help
No
Test strategy: Help
Sanger Sequencing of DNA
Pre-test genetic counseling required: Help
No
Post-test genetic counseling required: Help
No
Recommended fields not provided:
Test Order Code, How to Order, Lab contact for this test
Conditions Help
Total conditions: 1
Condition/Phenotype Identifier
Test Targets
Genes Help
Total genes: 1
Gene Associated Condition Germline or Somatic Allele (Lab-provided) Variant in NCBI
Methodology
Total methods: 1
Method Category Help
Test method Help
Instrument
Mutation scanning of the entire coding region
Bi-directional Sanger Sequence Analysis
ThermoFisher Genetic Analyzer SeqStudio
Clinical Information
Test purpose: Help
Diagnosis; Mutation Confirmation; Therapeutic management
Clinical validity: Help
The clinical validity of the test is high; there is significant variability in disease expression even among patients with the same genotype. Family studies have reported asymptomatic mutation carriers.
View citations (1)
  • doi: 10.1007/s10875-024-01681-1
Clinical utility: Help
Establish or confirm diagnosis
View citations (1)

Guidance for management
View citations (1)
  • doi: 10.1007/s10875-024-01681-1

Target population: Help
Patients with the haploinsufficiency of A20 (HA20) have been reported in populations of various ancestries
View citations (2)
  • Zhou Q, Wang H, Schwartz DM, Stoffels M, Park YH, Zhang Y, Yang D, Demirkaya E, Takeuchi M, Tsai WL, Lyons JJ, Yu X, Ouyang C, Chen C, Chin DT, Zaal K, Chandrasekharappa SC, Hanson EP, Yu Z, Mullikin JC, Hasni SA, Wertz IE, Ombrello AK, Stone DL, Hoffmann P, Jones A, Barham BK, Leavis HL, van Royen-Kerkof A, Sibley C, Batu ED, Gül A, Siegel RM, Boehm M, Milner JD, Ozen S, Gadina M, Chae J, Laxer RM, Kastner DL, Aksentijevich I. Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease. Nat Genet. 2016;48(1):67-73. doi:10.1038/ng.3459. Epub 2015 Dec 07. PMID: 26642243.
  • Aeschlimann FA, Batu ED, Canna SW, Go E, Gül A, Hoffmann P, Leavis HL, Ozen S, Schwartz DM, Stone DL, van Royen-Kerkof A, Kastner DL, Aksentijevich I, Laxer RM. A20 haploinsufficiency (HA20): clinical phenotypes and disease course of patients with a newly recognised NF-kB-mediated autoinflammatory disease. Ann Rheum Dis. 2018;77(5):728-735. doi:10.1136/annrheumdis-2017-212403. Epub 2018 Jan 09. PMID: 29317407.
Variant Interpretation:
What is the protocol for interpreting a variation as a VUS? Help
We suggest testing the patient's parents to determine whether the VUS identified in the patient is clinically significant or a rare polymorphism in the family.

Are family members with defined clinical status recruited to assess significance of VUS without charge? Help
Yes.

Will the lab re-contact the ordering physician if variant interpretation changes? Help
Yes.
Recommended fields not provided:
Is research allowed on the sample after clinical testing is complete?, Sample negative report, Sample positive report
Technical Information
Test Confirmation: Help
Positive results are confirmed on a new DNA preparation from the same blood sample using bi-directional Sanger sequencing.
Availability: Help
Tests performed
Entire test performed in-house
Analytical Validity: Help
This mutation detection method has 99% sensitivity to detect small nucleotide changes in the TNFAIP3 gene.
Proficiency testing (PT):
Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Inter-Laboratory

PT Provider: Help
European Molecular Genetics Quality Network, EMQN
VUS:
Software used to interpret novel variations Help
Sequencher

Laboratory's policy on reporting novel variations Help
Novel variants will be reported as VUS until family segregation studies are completed, or VUS is confirmed pathogenic based on functional validation.
Recommended fields not provided:
Assay limitations, Description of internal test validation method, Citations for Analytical validity, Description of PT method, Major CAP category, CAP category, CAP test list
Regulatory Approval
FDA Review: Help
Category: Not Applicable
Additional Information

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.