Secondary findings in 443 exome sequencing data

Area of Science:

• Genomics
• Medical Genetics
• Clinical Diagnostics

Background:

• Exome sequencing (ES) can reveal secondary genetic findings unrelated to the primary indication for testing.
• These secondary findings, particularly in medically actionable genes, hold significant potential for patient care and disease prevention.

Purpose of the Study:

• To evaluate the utility of exome sequencing for identifying medically actionable secondary findings in patients with neurological disorders.
• To classify and report variants according to established American College of Medical Genetics (ACMG) guidelines.

Main Methods:

• Analyzed 81 American College of Medical Genetics (ACMG) medically actionable genes in 443 patients with various neurological disorders using exome sequencing.
• Classified identified variants based on the 2015 ACMG Standards and Guidelines and ACMG recommendations for reporting secondary findings (v3.2).

Main Results:

• Detected 17 variants in 17 patients across 9 different genes, classified as secondary findings.
• Identified heterozygous variants in cancer-related genes (BRCA1, MSH2, PALB2), cardiovascular genes (MYH7, TTN, LDLR, DSC2, DSP), and a miscellaneous gene (TTR).
• Classified 13 variants as known pathogenic and 4 as expected pathogenic.

Conclusions:

• Exome sequencing effectively identifies medically actionable secondary findings in patients with neurological conditions.
• These findings have implications for preventing severe morbidity and mortality, offering valuable genetic insights.
• Supports the integration of secondary finding analysis into routine genetic testing protocols.