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Advances in genome sequencing have resulted in the identification of the causes for numerous rare diseases. However, many cases remain unsolved with standard molecular analyses. We describe a family presenting with a phenotype resembling inherited thrombocytopenia 2 (THC2). THC2 is generally caused by single nucleotide variants that prevent silencing of ANKRD26 expression during hematopoietic differentiation. Short-read whole-exome and genome sequencing approaches were unable to identify a causal variant in this family. Using long-read whole-genome sequencing, a large complex structural variant involving a paired-duplication inversion was identified. Through functional studies, we show that this structural variant results in a pathogenic gain-of-function WAC-ANKRD26 fusion transcript. Our findings illustrate how complex structural variants that may be missed by conventional genome sequencing approaches can cause human disease., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2021 Wahlster et al.)

Even when people perform tasks poorly, they often report unrealistically positive estimates of their own abilities in these situations. To better understand the origins of such overconfidence, we investigated whether it could be predicted by individual differences in working memory, attentional control, and self-reported trait impulsivity. Overconfidence was estimated by contrasting objective and subjective measures of situation awareness (the ability to perceive and understand task-relevant information in the environment), acquired during a challenging air traffic control simulation. We found no significant relationships between overconfidence and either working memory or attentional control. However, increased impulsivity significantly predicted greater overconfidence. In addition, overall levels of overconfidence were lower in our complex task than in previous studies that used less-complex lab-based tasks. Our results suggest that overconfidence may not be linked to high-level cognitive abilities, but that dynamic tasks with frequent opportunities for performance feedback may reduce misconceptions about personal performance., (Copyright © 2019 Elsevier Inc. All rights reserved.)