Introduction – Secondary findings (SF) are offered to patients and their families as an optional component of exome or genome testing. Reporting SF provides individuals with the opportunity to receive actionable results unrelated to the primary indication for testing, which may help prevent or reduce disease through early detection. This study evaluates trends in SF orders and reported results, with a focus on the impact of issuing independent reports for each tested individual rather than relying solely on proband findings.
Methods – We performed a retrospective review of SF in probands and their families who underwent exome testing at a single clinical laboratory between 2016 and 2024. Although the ACMG list of SF genes has evolved over time, diagnostic rates and the most frequently reported conditions have remained relatively stable.
Results – Of the 15,492 probands that received exome sequencing, 13,423 (86.6%) opted to receive secondary findings, with an average positive rate of 2.9% (n = 388/12,441). From 2016 to 2024, opt-in rates and positive SF rates remained relatively stable year-over-year. The prenatal group had the lowest opt-in rate at 74.3% (n=124/167). Among age-based groups, opt-in rates increased progressively: <1 year (82.6%; n=1,018/1233), 1–5 years (86.2%; n=4,963/5,758), 6–10 years (87.0%; n=2,666/3,065), 11–18 years (87.1%; n=2,590/2,973), 19–35 years (89.2%; 1,170/1,311), 36–50 years (90.0%; n=506/562), and 51+ years, which had the highest rate at 91.3% (n=387/424). This pattern indicates an upward trend in opt-in rates with increasing age among probands. In this cohort, SF analysis included independent analysis and reporting for up to three family members. This enables analysis of variants reported in parent reports regardless of whether the variant was detected in proband. For both parents and probands, variants in BRCA2 were the most commonly reported, followed by LDLR and BRCA1. Cancer predisposition was the leading genetic condition reported in secondary findings. Opt-in rates were similar between probands and parents (mothers: 86.8%, n = 10,518/12,117; fathers: 85.2%, n = 8,797/10,327), and positive rates were likewise comparable (mothers: 2.2%, n = 229/10,518; fathers: 2.4%, n = 215/8,797). Interestingly, 43.7% of mothers (n = 100/229) and 45.2% of fathers (n = 97/215) received positive results that were different than the proband, highlighting the value of laboratories offering independent secondary finding testing and reporting for each person tested. Among all SF orders, 66.7% (n = 8,960/13,423) were from parent-proband trios, while 3.4% (n = 459/13,423) were from non-parental trios. In parent-proband trios, 13.2% (n = 32/243) of positive secondary findings were confirmed to be de novo. Notably, 1.00% (n =100/10,049) of mothers had a SF that was not present in the proband. Similarly, 1.2% (n = 97/8,406) of fathers had a different variant than their child who opted in.
Conclusion – Providing each individual with their own report is an important step toward supporting informed patient care. If reporting were limited to the proband’s results, many parents with positive findings might not learn about their secondary findings, reducing opportunities for timely intervention. Separate reports with each individual’s unique results promote transparency and encourage proactive health decisions. Alternative approaches may reduce these benefits and limit the potential impact of genetic testing.
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