• 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




Associated disorders

The ATM gene is associated with an increased risk for autosomal dominant breast, pancreatic and prostate cancers (PMID: 15928302, 15942625, 16998505, 22585167, 26483394, 26662178, 27433846, 27324988, 27989354) and autosomal recessive ataxia-telangiectasia (A-T) (MedGen UID: 439).

The gene ATM (ataxia telangiectasia mutated) encodes a protein that is an important cell cycle checkpoint kinase that phosphorylates. It functions as a regulator of a wide variety of downstream proteins, including tumor-suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNArepair protein NBS1. This protein and closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways required for cell response to DNA damage and for genome stability.

ATM heterozygote
MedGen UID: 87542

Clinical condition
Women who are carriers of a single pathogenic ATM variant have an increased risk of breast cancer that ranges between 17–60% risk of breast cancer (PMID: 11830610, 16832357, 15928302, 16998505, 3574400, 16832357, 15880680, 16958054, 1961222, 21787400, 26662178, 27595995). Men with a single pathogenic variant in ATM have an increased risk of prostate cancer (PMID: 27433846, 18565893, 15280931, 17502119, 24556621), and both men and women have an increased risk of pancreatic cancer, although specific risks estimates are not yet established (PMID: 22585167, 26098866, 26483394). There may also be risks for other cancer types, however the current evidence is limited and emerging (PMID: 25622547, 15928302, 18565893, 21396839).

There is also evidence to suggest an association between ATM and colorectal cancer, and is therefore available as a “preliminary-evidence” gene on the Invitae Colorectal Cancer Syndrome Panel (PMID: 15928302, 15942625). Preliminary-evidence genes are selected from an extensive review of the literature and expert recommendations, but the association between the gene and the specific condition has not yet been completely established. This uncertainty may be resolved as new information becomes available, and therefore clinicians may continue to order these preliminary-evidence genes. There may also be risks for other cancer types among individuals with a single pathogenic ATM variant, however the current evidence is limited and emerging (PMID: 25622547, 15928302, 18565893, 21396839).

Gene information
The protein encoded by the ATM gene belongs to the PI3/PI4-kinase family. This protein is an important cell-cycle checkpoint kinase that phosphorylates. It functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint-signaling pathways that are required for cell response to DNA damage and for genome stability (NCBI Gene. Gene ID: 472. http://www.ncbi.nlm.nih.gov/gene/472. Accessed March 2018). If there is a pathogenic variant in this gene that prevents it from functioning normally, the risk of developing certain cancers may be increased.

Hereditary predisposition to cancer due to pathogenic variants in the ATM gene has autosomal dominant inheritance. This means that an individual with a pathogenic variant has a 50% chance of passing the condition on to their offspring. Once a pathogenic mutation is detected in an individual, it is possible to identify at-risk relatives who can pursue testing for this specific familial variant. Many cases are inherited from a parent, but some cases can occur spontaneously (i.e., an individual with a pathogenic variant who has parents who do not have it).

Individuals with a single pathogenic variant in ATM are also carriers of ataxia-telangiectasia (A-T). A-T is an autosomal recessive condition that results when an individual inherits a pathogenic ATM variant from each parent. Features include progressive cerebellar ataxia, oculomotor apraxia, choreoathetosis, telangiectasias of the conjunctivae, immunodeficiency, premature aging, endocrine abnormalities, and increased risk for malignancy—particularly leukemia and lymphoma (PMID: 20301790, 15279807, 26050521). For there to be a risk of A-T in offspring, both the patient and his/her partner would each have to carry a pathogenic variant in ATM. In this case, the risk of having have an affected child would be 25%.

Medical management guidelines and surveillance recommendations
The National Comprehensive Cancer Network® (NCCN®) has published screening and surveillance guidelines for women with a single pathogenic variant in ATM (NCCN. Genetic/Familial High-Risk Assessment: Breast and Ovarian. Version 1.2018):


  • Annual mammography with consideration of tomosynthesis starting at 40 years of age
  • Consider annual breast MRI with contrast starting at age 40, with modification as appropriate based on family history or specific gene mutation
  • Prophylactic risk-reducing mastectomy: evidence insufficient; manage based on family history. Insufficient evidence to recommend against radiation therapy.
  • Counsel for risk of autosomal recessive condition in offspring.

There has been some debate as to whether ionizing radiation is considered significantly carcinogenic to individuals with a single pathogenic ATM variant. There is currently no substantial evidence to suggest there are additional side effects from ionizing radiation compared to those who do not have an ATM pathogenic variant (PMID: 26662178, NCCN. Genetic/Familial High-Risk Assessment: Breast and Ovarian. Version 1.2018).

NCCN® cites insufficient evidence to warrant screening for prostate and pancreatic cancer (NCCN. Genetic/Familial High-Risk Assessment: Breast and Ovarian. Version 1.2018). In contrast, the American College of Gastroenterology Clinical Guidelines recommend pancreatic cancer screening for individuals with a single pathogenic ATM variant be limited to those with a first- or second-degree relative affected with pancreatic cancer. Ideally, screening should be performed in experienced centers utilizing a multidisciplinary approach under research conditions. Recommended screening includes annual endoscopic ultrasound and/or MRI of the pancreas starting at age 50 or 10 years younger than the earliest age of pancreatic cancer diagnosis in the family (PMID: 25645574).

An individual’s cancer risk and medical management are not determined by genetic test results alone. Overall cancer risk assessment incorporates additional factors, including personal medical history, family history, and any available genetic information that may result in a personalized plan for cancer prevention and surveillance.

Knowing if a pathogenic ATM variant is present is advantageous. At-risk relatives can be identified, enabling pursuit of a diagnostic evaluation. Further, the available information regarding hereditary cancer susceptibility genes is constantly evolving and more clinically relevant data regarding this gene are likely to become available in the near future. Awareness of this cancer predisposition encourages patients and their providers to inform at-risk family members, to diligently follow recommended screening protocols, and to be vigilant in maintaining close and regular contact with their local genetics clinic in anticipation of new information.

Additional reference
Referenced with permission from the NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian. Version 1.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed February, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org.

The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a statement of consensus of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Review date: February 2018

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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

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