Deficiency of ADA2 - Clinical Genetic Test - GTR

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Deficiency of ADA2

Clinical Genetic Test

offered by

Inflammatory Disease Section/Clinical Genetics Service

GTR Test Accession: GTR000529105.5

INHERITED DISEASECONNECTIVE TISSUESYNDROMIC DISEASE ... View more

Last updated in GTR: 2024-07-08

Last annual review date for the lab: 2024-07-12

At a Glance

Test purpose:

Diagnosis; Mutation Confirmation; Pre-symptomatic; ...

Conditions (1):

Deficiency of adenosine deaminase 2

Genes (1):

ADA2 (22q11.1)

Methods (1):

Molecular Genetics - Mutation scanning of the entire coding region: Bi-directional Sanger Sequence Analysis

Target population:

Patients with systemic inflammation, systemic vasculitis, polyarteritis nodosa

Clinical validity:

Identification of two pathogenic or likely pathogenic variants in ADA2 …

Clinical utility:

Establish or confirm diagnosis; Guidance for management

Ordering Information

Offered by:

Inflammatory Disease Section/Clinical Genetics Service

Test short name:

DADA2

Specimen Source:

Buccal swab
Isolated DNA
Peripheral (whole) blood

Who can order:

Genetic Counselor
Health Care Provider
Licensed Physician
Nurse Practitioner

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:

Blood sample in an EDTA tube could be shipped at room temperature

Test service:

Clinical Testing/Confirmation of Mutations Identified Previously

Test development:

Test developed by laboratory but exempt from FDA oversight (eg. NYS CLEP approved, offered within a hospital or clinic)

Informed consent required:

Test strategy:

Sanger sequencing of DNA

Pre-test genetic counseling required:

Post-test genetic counseling required:

Recommended fields not provided:

Test Order Code, Lab contact for this test

Conditions

Total conditions: 1

Condition/Phenotype	Identifier

Test Targets

Genes

Total genes: 1

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

Methodology

Total methods: 1

Method Category

Test method

Instrument

Mutation scanning of the entire coding region

Bi-directional Sanger Sequence Analysis

ThermoFisher Genetic Analyzer SeqStudio

Clinical Information

Test purpose:

Diagnosis; Mutation Confirmation; Pre-symptomatic; Therapeutic management

Clinical validity:

Identification of two pathogenic or likely pathogenic variants in ADA2 confirms the clinical diagnosis of DADA2. In case only one pathogenic or likely pathogenic variant is identified, we recommend biochemical testing for deficiency of ADA2. Search for a disease-causing variant in non-coding regions requires more complex testing and analysis.

View citations (1)

https://pubmed.ncbi.nlm.nih.gov/31393689

Clinical utility:

Establish or confirm diagnosis

View citations (1)

doi: 10.1001/jamanetworkopen.2023.15894

Guidance for management

View citations (1)

Digitoxin metabolism by rat liver microsomes. Schmoldt A, et al. Biochem Pharmacol. 1975;24(17):1639-41. doi:10.1042/bj1490749. PMID: 10.1001/jamanetworkopen.2023.15894.

Target population:

Patients with systemic inflammation, systemic vasculitis, polyarteritis nodosa

View citations (2)

Zhou Q, Yang D, Ombrello AK, Zavialov AV, Toro C, Zavialov AV, Stone DL, Chae JJ, Rosenzweig SD, Bishop K, Barron KS, Kuehn HS, Hoffmann P, Negro A, Tsai WL, Cowen EW, Pei W, Milner JD, Silvin C, Heller T, Chin DT, Patronas NJ, Barber JS, Lee CC, Wood GM, Ling A, Kelly SJ, Kleiner DE, Mullikin JC, Ganson NJ, Kong HH, Hambleton S, Candotti F, Quezado MM, Calvo KR, Alao H, Barham BK, Jones A, Meschia JF, Worrall BB, Kasner SE, Rich SS, Goldbach-Mansky R, Abinun M, Chalom E, Gotte AC, Punaro M, Pascual V, Verbsky JW, Torgerson TR, Singer NG, Gershon TR, Ozen S, Karadag O, Fleisher TA, Remmers EF, Burgess SM, Moir SL, Gadina M, Sood R, Hershfield MS, Boehm M, Kastner DL, Aksentijevich I. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med. 2014;370(10):911-20. doi:10.1056/NEJMoa1307361. Epub 2014 Feb 19. PMID: 24552284.
Navon Elkan P, Pierce SB, Segel R, Walsh T, Barash J, Padeh S, Zlotogorski A, Berkun Y, Press JJ, Mukamel M, Voth I, Hashkes PJ, Harel L, Hoffer V, Ling E, Yalcinkaya F, Kasapcopur O, Lee MK, Klevit RE, Renbaum P, Weinberg-Shukron A, Sener EF, Schormair B, Zeligson S, Marek-Yagel D, Strom TM, Shohat M, Singer A, Rubinow A, Pras E, Winkelmann J, Tekin M, Anikster Y, King MC, Levy-Lahad E. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med. 2014;370(10):921-31. doi:10.1056/NEJMoa1307362. Epub 2014 Feb 19. PMID: 24552285.

Variant Interpretation:

What is the protocol for interpreting a variation as a VUS?
We suggest testing close family members, including unaffected parents and siblings, to segregate the inheritance of VUS in the family.

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

Will the lab re-contact the ordering physician if variant interpretation changes?
Yes. Referring physician will be contacted only if there is unambiguous evidence about the pathogenicity of previously reported VUS

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:

Positive results are confirmed on a new DNA preparation from the same blood sample using bi-directional Sanger sequencing.

Availability:

Tests performed
Entire test performed in-house

Analytical Validity:

This assay has 99% sensitivity to detect single nucleotide variations.

Assay limitations:

This assay cannot identify mutations outside of the coding region (e.g., deep intronic variants or variants in regulatory regions). Testing for those variants requires additional, more complex analyses.

Proficiency testing (PT):

Is proficiency testing performed for this test?
Yes

Method used for proficiency testing:
Intra-Laboratory

PT Provider:
European Molecular Genetics Quality Network, EMQN

VUS:

Software used to interpret novel variations
Sequencher

Laboratory's policy on reporting novel variations
Novel variants will be reported as VUS until a family-based study is completed.

Recommended fields not provided:

Citations to support 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:

Category: Not Applicable

Additional Information

Reviews:

PubMed Clinical Queries

Clinical resources:

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.