Collaborator: Albert Einstein College of Medicine
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Improved, ACMG-compliant, in silico prediction of pathogenicity for missense substitutions encoded by TP53 variants
Abstract Clinical interpretation of germline missense variants represents a major challenge, including those in the TP53 Li–Fraumeni syndrome gene. Bioinformatic prediction is a key part of variant classification strategies. We aimed to optimize the performance of the Align‐GVGD tool used for p53 missense variant prediction, and compare its performance to other bioinformatic tools (SIFT, PolyPhen‐2) and ensemble…
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Polygenic risk score for breast cancer in high-risk women
Speaker: Celine Vachon, MD. PhD (Mayo Clinic) We evaluated a 100-SNP polygenic risk score (PRS) in a high-risk patient population of Caucasian women referred for genetic testing, to determine the extent to which the PRS is predictive of breast cancer. The PRS was significantly higher in cases than controls (mean±SD 1.20±0.88 vs. 0.95±0.69, p<0.0001). The…
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A survey of current practices for genomic sequencing test interpretation and reporting processes in US laboratories
Abstract Purpose While the diagnostic success of genomic sequencing expands, the complexity of this testing should not be overlooked. Numerous laboratory processes are required to support the identification, interpretation, and reporting of clinically significant variants. This study aimed to examine the workflow and reporting procedures among US laboratories to highlight shared practices and identify areas…
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Frequency of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls
Abstract Objectives Given the lack of adequate screening modalities, knowledge of ovarian cancer risks for carriers of pathogenic alterations in predisposition genes is important for decisions about risk-reduction by salpingo-oophorectomy. We sought to determine which genes assayed on multi-gene panels are associated with ovarian cancer, the magnitude of the associations, and for which clinically meaningful…
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Clinical laboratories collaborate to resolve differences in variant interpretations submitted to ClinVar
Abstract Purpose Data sharing through ClinVar offers a unique opportunity to identify interpretation differences between laboratories. As part of a ClinGen initiative, four clinical laboratories (Ambry, GeneDx, Partners Healthcare Laboratory for Molecular Medicine, and University of Chicago Genetic Services Laboratory) collaborated to identify the basis of interpretation differences and to investigate if data sharing and…
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Classification of variants of uncertain significance in BRCA1 and BRCA2 using personal and family history of cancer from individuals in a large hereditary cancer multigene panel testing cohort
Abstract Purpose Genetic testing of individuals often results in identification of genomic variants of unknown significance (VUS). Multiple lines of evidence are used to help determine the clinical significance of these variants. Methods We analyzed ~138,000 individuals tested by multigene panel testing (MGPT). We used logistic regression to predict carrier status based on personal and…