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  • Test code: 01724
  • 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 Ataxia-Telangiectasia Test

Test description

This test analyzes the ATM gene, which is associated with ataxia-telangiectasia (A-T). Individuals with pathogenic variants in both copies of the ATM gene can develop A-T, a condition characterized by childhood-onset progressive cerebellar ataxia, oculomotor apraxia, choreoathetosis, telangiectasias of the conjunctivae, immunodeficiency, and increased risk for malignancy—particularly leukemia and lymphoma. There is evidence to suggest that women who are carriers of a single pathogenic ATM variant have a 17%-52% risk of breast cancer. The risk for other cancers may be elevated in carriers as well, including pancreatic cancer, although the specific risk is currently unclear.

Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

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Primary panel (1 gene)

Alternative tests to consider

ATM can also be ordered as part of a larger panel to test for different types of hereditary cancer conditions. Depending on the individual’s clinical and family history, one of these larger panels may be appropriate. Any of these larger panels can be ordered for no additional charge.

  • ataxia-telangiectasia (A-T)

Ataxia-telangiectasia (A-T) is characterized by the onset of progressive cerebellar ataxia in early childhood, oculomotor apraxia, choreoathetosis, telangiectasias of the conjunctivae, immunodeficiency, and increased risk for malignancy—particularly leukemia and lymphoma. Affected individuals are particularly sensitive to ionizing radiation. Serum AFP concentration is elevated above 10 ng/mL in more than 95% of cases. Other features include premature aging and endocrine abnormalities.

There is evidence to suggest that women who are carriers of a single pathogenic ATM variant have a 17%-52% risk of breast cancer. The risk for other cancers, including pancreatic cancer, may be elevated in carriers as well, although the specific risk is currently unclear.

The risk for malignancy in individuals with A-T is approximately 38%. Leukemia and lymphoma account for approximately 85% of A-T-related malignancies. As affected individuals are living longer, other cancers such as ovarian, breast, stomach, melanoma, leiomyomas, and sarcomas have been observed.

The breast cancer risk for heterozygous carriers of a single pathogenic ATM variant is 17%-52%. There is also evidence to suggest ATM carriers have an increased risk of pancreatic cancer.

The ATM gene is the only gene known to be associated with A-T. Greater than 99% of individuals with classic A-T have pathogenic variants in ATM.

A-T is inherited in an autosomal recessive pattern. There is an increased risk for breast and possibly pancreatic cancer in individuals who carry a single pathogenic ATM variant.

The prevalence of A-T is estimated at 1 in 40,000 to 1 in 100,000 individuals.

Ataxia-telangiectasia (A-T) testing may be considered in individuals with the following:

  • progressive cerebellar dysfunction
    • head tilt
    • slurred speech
    • oculomotor apraxia
  • immunodeficiency
  • telangiectasias

  1. Ahmed, M, Rahman, N. ATM and breast cancer susceptibility. Oncogene. 2006; 25(43):5906-11. doi: 10.1038/sj.onc.1209873. PMID: 16998505
  2. Thompson, D, et al. Cancer risks and mortality in heterozygous ATM mutation carriers. J. Natl. Cancer Inst. 2005; 97(11):813-22. doi: 10.1093/jnci/dji141. PMID: 15928302
  3. Bakker, JL, de, Winter, JP. A role for ATM in hereditary pancreatic cancer. Cancer Discov. 2012; 2(1):14-5. doi: 10.1158/2159-8290.CD-11-0318. PMID: 22585162
  4. Renwick, A, et al. ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat. Genet. 2006; 38(8):873-5. doi: 10.1038/ng1837. PMID: 16832357
  5. Roberts, NJ, et al. ATM mutations in patients with hereditary pancreatic cancer. Cancer Discov. 2012; 2(1):41-6. doi: 10.1158/2159-8290.CD-11-0194. PMID: 22585167
  6. Swift, M, et al. Breast and other cancers in families with ataxia-telangiectasia. N. Engl. J. Med. 1987; 316(21):1289-94. doi: 10.1056/NEJM198705213162101. PMID: 3574400
  7. Gatti, R. Ataxia-Telangiectasia. 1999 Mar 19. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK26468/ PMID: 20301790
  8. Scott, SP, et al. Missense mutations but not allelic variants alter the function of ATM by dominant interference in patients with breast cancer. Proc. Natl. Acad. Sci. U.S.A. 2002; 99(2):925-30. doi: 10.1073/pnas.012329699. PMID: 11805335
  9. National Library of Medicine, Genetics Home Reference: Ataxia-telangiectasia. http://ghr.nlm.nih.gov/condition/ataxia-telangiectasia Accessed July 2015.
  10. Swift, M, et al. Incidence of cancer in 161 families affected by ataxia-telangiectasia. N. Engl. J. Med. 1991; 325(26):1831-6. PMID: 1961222

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
ATM NM_000051.3