Patient Clinical Profile

  • Patient Age: 32
  • Gender: Female
  • Personal Clinical History: No personal history of cancer
  • Visit type: Annual wellness exam

Myriad myRisk® Panel Test Result:

VUS in both ATM and CHEK2

Variation in the human genome is normal, with new genetic changes discovered every day. That’s why variants of uncertain significance (VUS) are expected in genetic testing. A VUS is a change in the genetic sequence for which association with disease risk is unclear. An uncertain genetic test result can be confusing to patients and make it challenging for health care providers to counsel patients on the appropriate course of management.
With over 20 years of experience, Myriad’s Variant Classification Program called myVision®, is committed to providing the most accurate test results to patients and their families. Learn the benefits of myVision through a Myriad myRisk® case study highlighted below.

Patient’s Family History

Relative Cancer Age of Dx
Paternal Aunt Breast 43
During a routine annual wellness exam, this patient’s new ObGyn not only collected a thorough cancer family history, but also acted on this information, noticing an early age of onset of breast cancer on the paternal side of patient’s family. Since this patient met NCCN BRCA1/2 testing criteria by having a second degree relative with breast cancer ≤ 451, the clinician ordered a Myriad myRisk hereditary cancer panel to help determine this patient’s cancer risks.Based on these VUS test results, the patient is advised to follow medical management based on her personal and family history of cancer. Because of Myriad’s lifetime commitment to patients and their families, Myriad offered targeted genetic testing at no cost to selected family members of this patient to gather information about her VUS results and assist in the reclassification process. Her CHEK2 VUS was later reclassified as suspected deleterious and the ATM VUS reclassified to a variant of no clinical significance. An amended report was sent by Myriad to the ObGyn, allowing her to contact this patient and review her reclassified, clinically actionable result.

Why this matters:

  • We now know this patient has up to a 48% lifetime risk of developing breast cancer compared to 10.2% risk for general population2-5
  • Up to a 29% risk of developing a second primary within 10 years of the first breast cancer diagnosis6
  • Possibly elevated risk for colorectal cancer7

NCCN CHEK2 Cancer Risk Management Recommendations

  • Breast awareness – Women should be familiar with their breasts and promptly report changes to their healthcare provider. Periodic, consistent breast self-examination (BSE) may facilitate breast awareness.8
  • Clinical encounter, including clinical breast exam, ongoing risk assessment and risk reduction counseling every 6 to 12 months.8
  • Annual mammography and consideration of breast MRI with contrast beginning at age 40, or modified to a younger age based on the family history of breast cancer1
  • Consider additional risk-reduction strategies1,8
  • Colonoscopy screening every 5 years, beginning at age 40 or 10 years younger than the age of diagnosis for any first-degree relative with colorectal cancer7

Bottom Line

This case demonstrates the importance of a diagnostic test to stratify a patient’s risk to develop cancer. Without the reclassified test result, this patient would not have known that she is at risk for cancers other than those seen in her family history. She can now avoid a cancer diagnosis through earlier and more frequent surveillance, chemoprevention, and preventive surgery.

Learn More About the myVisionTM Variant Classification Program



  1. Daly M et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast and Ovarian. V 2.2017. December 07. Available at
  2. Weischer et al. CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls. J Clin Oncol. 2008 26: 542-8.
  3. CHEK2 Breast Cancer Case-Control Consortium. CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet. 2004 74:1175-82.
  4. Weischer M, et al. CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer. J Clin Oncol. 2012 30:4308-16.
  5. Meijers-Heijboer H, et al. CHEK2-Breast Cancer Consortium. Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet. 2002 31:55-9.
  6. Kriege M, et al. Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy. Br J Cancer. 2014. 111:1004-13.
  7. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 2.2016. September 26. Available at
  8. Bevers TB, et al. NCCN Clinical Practice Guidelines in Oncology®: Breast Cancer Screening and Diagnosis. V 1.2016. July 27. Available at

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