Coastal wave storms pose a massive threat to over 10% of the world's population now inhabiting the low elevation coastal zone and to the trillions of $ worth of coastal zone infrastructure and developments therein. Using a ~ 40-year wave hindcast, we here present a world-first assessment of wind-wave storminess along the global coastline. Coastal regions are ranked in terms of the main storm characteristics, showing Northwestern Europe and Southwestern South America to suffer, on average, the most intense storms and the Yellow Sea coast and the South-African and Namibian coasts to be impacted by the most frequent storms. These characteristics are then combined to derive a holistic classification of the global coastlines in terms of their wave environment, showing, for example, that the open coasts of northwestern Europe are impacted by more than 10 storms per year with mean significant wave heights over 6 m. Finally, a novel metric to classify the degree of coastal wave storminess is presented, showing a general latitudinal storminess gradient. Iceland, Ireland, Scotland, Chile and Australia show the highest degree of storminess, whereas Indonesia, Papua-New Guinea, Malaysia, Cambodia and Myanmar show the lowest.
Skipping of BRCA2 exon 3 (∆E3) is a naturally occurring splicing event, complicating clinical classification of variants that may alter ∆E3 expression. This study used multiple evidence types to assess pathogenicity of 85 variants in/near BRCA2 exon 3. Bioinformatically predicted spliceogenic variants underwent mRNA splicing analysis using minigenes and/or patient samples. ∆E3 was measured using quantitative analysis. A mouse embryonic stem cell (mESC) based assay was used to determine the impact of 18 variants on mRNA splicing and protein function. For each variant, population frequency, bioinformatic predictions, clinical data, and existing mRNA splicing and functional results were collated. Variant class was assigned using a gene-specific adaptation of ACMG/AMP guidelines, following a recently proposed points-based system. mRNA and mESC analysis combined identified six variants with transcript and/or functional profiles interpreted as loss of function. Cryptic splice site use for acceptor site variants generated a transcript encoding a shorter protein that retains activity. Overall, 69/85 (81%) variants were classified using the points-based approach. Our analysis shows the value of applying gene-specific ACMG/AMP guidelines using a points-based approach and highlights the consideration of cryptic splice site usage to appropriately assign PVS1 code strength.