Background The recent development and enormous application of parallel sequencing technology in oncology has produced immense amounts of cell-specific genetic information. However, publicly available cell-specific genetic variants are not explained by well-established guidelines. Additionally, cell-specific variants interpretation and classification has remained a challenging task and lacks standardization. The Association for Molecular Pathology (AMP), the American Society of Clinical Oncology (ASCO), and the College of American Pathologists (CAP) published the first consensus guidelines for cell-specific variants cataloging and clinical annotations. Methods AMP–ASCO–CAP recommended sources and information were downloaded and used as follows: relative knowledge in oncology clinical practice guidelines; approved, investigative or preclinical drugs; supporting literature and each gene-tumor site correlation. All information was homogenized into a single knowledgebase. Finally, we incorporated the consensus recommendations into a new computational method. Results A subset of cancer genetic variants was manually curated to benchmark our method and well-known computational algorithms. We applied the new method on freely available tumor-specific databases to produce a clinically actionable cancer somatic variants (CACSV) dataset in an easy-to-integrate format for most clinical analytical workflows. The research also showed the current challenges and limitations of using different classification systems or computational methods. Conclusion CACSV is a step toward cell-specific genetic variants standardized interpretation as it is readily adaptable by most clinical laboratory pipelines for somatic variants clinical annotations. CACSV is freely accessible at (https://github.com/tsobahytm/CACSV/tree/main/dataset).

In this case study, we reported a case of 8-year-old Saudi patient diagnosed with polysplenia, situs inversus totalis and double outlet right ventricle. We identified five novel missense mutation in three genes GATA4, NIPBL and APC as causative mutations and could be used for early detecting of polysplenia syndrome.Hosted file Polysplenis case revised 14-4-2020[2602] 24-04-2020.pdf available at https://authorea.com/users/315337/articles/44 novel-genomic-variants-associated-with-polysplenia-situs-inversus-totalis-atrial-septal-defect-and-double-outletright-ventricle-in-saudi-patient Hosted file Figures for the Polysplenis case 10-4-2020.docx available at https://authorea.com/users/315337/articles/445720novel-genomic-variants-associated-with-polysplenia-situs-inversus-totalis-atrial-septal-defect-and-double-outletright-ventricle-in-saudi-patient

Background:The recent development and enormous application of parallel sequencing technology inoncology have produced immense cell-specific genetic data. However, publicly available cell-specific genetic variants are not explained by well-established guidelines. Additionally, cell-specific variants interpretation and classification has remained a challenging task, and lacksstandardization. The Association for Molecular Pathology (AMP), American Society of ClinicalOncology (ASCO), and College of American Pathologists (CAP) published the first consensusguidelines for cell-specific variants cataloging and clinical interpretation.Results:We developed a new method that followed the consensus recommendations, and applied ourmethod on open source tumor-specific databases to produce clinically actionable cancersomatic variants (CACSV) dataset in integratable formats by most clinical analytical workflows.We evaluated our method with well-known classification algorithms, and found the new methodto be comparable and more adhering to the recent guidelines.Conclusion:CACSV is a step toward cell-specific genetic variants universal interpretation, readily adaptableby most clinical laboratories pipelines and can escalate somatic variants elucidation andclassification. CACSV is made free available (https://github.com/tsobahytm/CACSV/tree/main/dataset).