Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jan 14;10(1):223.
doi: 10.1038/s41598-019-57080-9.

Challenges in reporting pathogenic/potentially pathogenic variants in 94 cancer predisposing genes - in pediatric patients screened with NGS panels

Adela Chirita-Emandi  1   2 , Nicoleta Andreescu  3   4 , Cristian G Zimbru  3   5 , Paul Tutac  3   4 , Smaranda Arghirescu  6   7 , Margit Serban  7 , Maria Puiu  3   4
Affiliations

Challenges in reporting pathogenic/potentially pathogenic variants in 94 cancer predisposing genes - in pediatric patients screened with NGS panels

Adela Chirita-Emandi et al. Sci Rep. .

Abstract

The benefit of reporting unsolicited findings in Next Generation Sequencing (NGS) related to cancer genes in children may have implications for family members, nevertheless, could also cause distress. We aimed to retrospectively investigate germline variants in 94 genes implicated in oncogenesis, in patients referred to NGS testing for various rare genetic diseases and reevaluate the utility of reporting different classes of pathogenicity. We used in silico prediction software to classify variants and conducted manual review to examine unsolicited findings frequencies in 145 children with rare diseases, that underwent sequencing - using a 4813 gene panel. The anonymized reanalysis revealed 18250 variants, of which 126 were considered after filtering. Six pathogenic variants (in BRCA1,BMPR1A,FANCA,FANCC,NBN genes) with cancer related phenotype and three unsolicited variants (in BRCA2,PALB2,RAD50 genes) were reported to patients. Additionally, three unsolicited variants in ATR, BLM (in two individuals), and FANCB genes presented potential cancer susceptibility, were not reported to patients. In retrospect, 4.8% (7/145) of individuals in our cohort had unsolicited NGS findings related to cancer. More efforts are needed to create an updatable consensus in reporting variants in cancer predisposing genes, especially for children. Consent process is crucial to inform of both value and risk of additional genetic information.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

References

    1. Kalia SS, et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet. Med. 2017;19:249–255. doi: 10.1038/gim.2016.190. - DOI - PubMed
    1. Green RC, et al. ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing. Genet Med. 2013;15:565–574. doi: 10.1038/gim.2013.73. - DOI - PMC - PubMed
    1. Townsend A, Adam S, Birch PH, Friedman JM. Paternalism and the ACMG recommendations on genomic incidental findings: patients seen but not heard. Genetics in Medicine. 2013;15:751–752. doi: 10.1038/gim.2013.105. - DOI - PubMed
    1. Richards S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 2015;17:405–424. doi: 10.1038/gim.2015.30. - DOI - PMC - PubMed
    1. Hehir-Kwa JY, et al. Towards a European consensus for reporting incidental findings during clinical NGS testing. Eur. J. Hum. Genet. 2015;23:1601–1606. doi: 10.1038/ejhg.2015.111. - DOI - PMC - PubMed

Publication types

Substances