Publications by authors named "S Palmer-Smith"
Purpose: Current practice is to report and manage likely pathogenic/pathogenic variants in a given cancer susceptibility gene as though having equivalent penetrance, despite increasing evidence of intervariant variability in risk associations. Using existing variant interpretation approaches, largely based on full-penetrance models, variants in which reduced penetrance is suspected may be classified inconsistently and/or as variants of uncertain significance. We aimed to develop a national consensus approach for such variants within the Cancer Variant Interpretation Group UK (CanVIG-UK) multidisciplinary network.
View Article and Find Full Text PDFBackground: The 2015 American College of Medical Genetics/Association of Molecular Pathology (ACMG/AMP) variant classification framework specifies that case-control observations can be scored as 'strong' evidence (PS4) towards pathogenicity.
Methods: We developed the PS4-likelihood ratio calculator (PS4-LRCalc) for quantitative evidence assignment based on the observed variant frequencies in cases and controls. Binomial likelihoods are computed for two models, each defined by prespecified OR thresholds.
Article Synopsis
- The study examines the integration of genomic data across NHS laboratories in England and Wales, highlighting variations in data structure, quality, and ease of local assembly for cancer susceptibility gene testing.
- A survey of 51 clinical scientists revealed significant differences in how variant data is transferred, formatted, and classified within Laboratory Information Management Systems (LIMS) across the participating labs.
- The findings indicate that current workflows are often inefficient and prone to errors due to their manual nature, suggesting that implementing recommended improvements could streamline data submission processes for better national and international collaboration.
Article Synopsis
- * A study identified 41 patients with this specific mutation, revealing that most present CALs and freckling, while 83% meet the NIH diagnostic criteria for NF1, but there’s a significant absence of neurofibromas and gliomas, with only one documented case of a subcutaneous neurofibroma.
- * Learning disabilities
Objective: To determine the frequency of germline and somatic pathogenic BRCA1 and BRCA2 variants in patients with high-grade serous ovarian cancer tested by next-generation sequencing (NGS), with the aim of defining the best strategy to be implemented in future routine testing.
Design: National retrospective audit.
Setting: The All Wales Medical Genomics Service (AWMGS).