Secondary findings from clinical genomic sequencing: prevalence, patient perspectives, family history assessment, and health-care costs from a multisite study

Abstract

Purpose: Clinical sequencing emerging in health care may result in secondary findings (SFs).

Methods: Seventy-four of 6240 (1.2%) participants who underwent genome or exome sequencing through the Clinical Sequencing Exploratory Research (CSER) Consortium received one or more SFs from the original American College of Medical Genetics and Genomics (ACMG) recommended 56 gene-condition pair list; we assessed clinical and psychosocial actions.

Results: The overall adjusted prevalence of SFs in the ACMG 56 genes across the CSER consortium was 1.7%. Initially 32% of the family histories were positive, and post disclosure, this increased to 48%. The average cost of follow-up medical actions per finding up to a 1-year period was $128 (observed, range: $0-$678) and $421 (recommended, range: $141-$1114). Case reports revealed variability in the frequency of and follow-up on medical recommendations patients received associated with each SF gene-condition pair. Participants did not report adverse psychosocial impact associated with receiving SFs; this was corroborated by 18 participant (or parent) interviews. All interviewed participants shared findings with relatives and reported that relatives did not pursue additional testing or care.

Conclusion: Our results suggest that disclosure of SFs shows little to no adverse impact on participants and adds only modestly to near-term health-care costs; additional studies are needed to confirm these findings.

Keywords: genomic sequencing; health-care resource utilization; secondary findings.

Conflict of interest statement

Conflict of Interest: LMA, BBB, CLB, JSB, KBB, KLB, KMB, SB, KDC, GMC, LKC, MCD, JNE, KME, CRF, AAG, MJG, KABG, LAH, MRH, GPJ, JJJ, JBK, TLK, WVK, KLL, ALM, CM, JO, EJR, AMS, NBS, ET, MLT, JLV, BSW, none; CSR and HLR are employed by a testing laboratory that offers commercially available sequencing. RCG receives compensation for consultation from AIA, Americord, Helix and Veritas; and is co-founder, advisor and equity holder in Genome Medical, Inc; and is employed by a testing laboratory that offers commercially available sequencing. LGB is an uncompensated advisor to the Illumina Corp, receives royalties from Genentech, Inc, and honoraria from Wiley-Blackwell. SEP is a member of the Scientific Advisory Panel of the Baylor Genetics Laboratory. DLV is a consultant to Roche Sequencing Systems.

Figures

Figure 1.

A) Unique variants reported following re-classification, which included downgraded variants. B) Gene-specific adjusted prevalence, which excluded downgraded variants originally disclosed as pathogenic or likely pathogenic. VUS: variant of uncertain significance LP: likely pathogenic P: pathogenic

Figure 2.

Family history known prior to result disclosure and following SF results disclosure