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

Hart MR1,2, Biesecker BB3, Blout CL4, Christensen KD4,5, Amendola LM6,7, Bergstrom KL8, Biswas S9, Bowling KM10, Brothers KB11, Conlin LK12,13, Cooper GM10, Dulik MC12,13, East KM10, Everett JN14,15, Finnila CR10, Ghazani AA16, Gilmore MJ17, Goddard KAB18, Jarvik GP6,7, Johnston JJ19, Kauffman TL18, Kelley WV10, Krier JB4, Lewis KL19, McGuire AL20, McMullen C18, Ou J7, Plon SE8, Rehm HL5,21,22, Richards CS23, Romasko EJ12, Miren Sagardia A3, Spinner NB12, Thompson ML10, Turbitt E3, Vassy JL4,5,24, Wilfond BS25, Veenstra DL7,26, Berg JS27, Green RC4,5,22,28, Biesecker LG19, Hindorff LA29.

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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.