2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Evaluating novel dosage sensitivity predictors for inclusion in the classification of recurrent copy number variants

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The document discusses the evaluation of dosage sensitivity predictors for the classification of recurrent copy number variants (CNVs). The study aimed to assess the utility of current and novel dosage sensitivity predictors in clinical CNV classification.<br /><br />The document provides tables and figures presenting the currently available dosage sensitivity predictors, including the Haploinsufficiency (HI) predictor, with specific cutoff values for different dosage predictors. It also includes a dosage sensitivity metric for recurrent CNV regions, with different evidence types and point requirements for scoring.<br /><br />The study evaluated the impact of incorporating the novel dosage sensitivity predictors, pHaplo and pTriplo, into the recurrent CNV metric. The results showed that using pHaplo as a measure for established dosage sensitive genes associated with early onset/highly penetrant conditions was more suitable than using the percentage of HI. Incorporating pTriplo into the metric resulted in some regions being scored more consistently and discrepancies with current scoring.<br /><br />However, the study also mentioned that additional regions and genes would need to be reviewed before incorporating pTriplo into the metric due to the lack of a secondary method to confirm its accuracy.<br /><br />Overall, the document provides information on the evaluation of dosage sensitivity predictors for the classification of recurrent CNVs and discusses the potential implications of incorporating novel predictors into the clinical CNV classification process.

Asset Subtitle

Presenting Author - John Herriges, PhD; Co-Author - Cassandra K. Runke, MS; Co-Author - Zoe K. Lewis, MS, CGC; Co-Author - Lucilla Pizzo, PhD; Co-Author - Bradley Coe, PhD; Co-Author - Laura K. Conlin, PhD; Co-Author - Benjamin A. Hilton, PhD; Co-Author - Brynn Levy, M.Sc.(Med).,PhD.; Co-Author - Andrea K. Vaags, PhD; Co-Author - Shulin Zhang, Ph.D.; Co-Author - Christa L. Martin; Co-Author - Erica F. Andersen, PhD, FACMG;

Meta Tag

Microarray

Molecular Cytogenetics

Co-Author Cassandra K. Runke, MS

Co-Author Zoe K. Lewis, MS, CGC

Co-Author Lucilla Pizzo, PhD

Co-Author Bradley Coe, PhD

Co-Author Laura K. Conlin, PhD

Co-Author Benjamin A. Hilton, PhD

Co-Author Brynn Levy, M.Sc.(Med).,PhD.

Co-Author Andrea K. Vaags, PhD

Co-Author Shulin Zhang, Ph.D.

Co-Author Christa L. Martin

Co-Author Erica F. Andersen, PhD, FACMG

Presenting Author John Herriges, PhD

Keywords

dosage sensitivity predictors

CNV classification

recurrent copy number variants

clinical

current predictors

novel predictors

Haploinsufficiency predictor

dosage sensitivity metric

pHaplo

pTriplo