PMC:6037202 / 52296-53610 JSONTXT

{"project":"2_test","denotations":[{"id":"29909963-26161383-2051644","span":{"begin":710,"end":712},"obj":"26161383"}],"text":"WGS identified six SVs predicted to affect a gene of interest, and two of these occurred in an individual whose personal or family history included tumors consistent with variants in that gene. The medical record showed no evidence that the individual with the PTEN inversion exhibited other features of constitutional variants in this gene, such as macrocephaly, as well as no record of an examination in a consultation where only BRCA1 and BRCA2 testing was anticipated. Although the numbers of potentially pertinent SVs are small, these aberrations are unlikely to be detected by panel or exome sequencing alone. Copy-number variation can be identified from the analysis of read counts in WES or panel data,52 but most diagnostic laboratories rely on techniques such as multiplex probe ligation assays (MLPAs) to test individual genes. If MLPA analysis is applied to many genes, then the cost could make WGS more economical than WES or panel-based testing, but investigating this would require a detailed cost-benefit analysis. Furthermore, WGS can detect inversions and translocations that are not characterized by MLPA. A note of caution, however, arises from a deletion involving BRCA2 exons 14–16; we were made aware of this deletion by the referring clinician, but it was not detected through our analyses."}