New and De Novo Biallelic Variant Associated With Owren's Disease: Precision Medicine in Blooding Disorders

Introduction Autosomal recessive coagulation factor V deficiency (1)causes moderate to severe bleeding (2). Currently, 450 clinically significant variants have been identified of the 3942 described.(2) Materials and methods 10-year-old female with 3 hospitalizations for dental extraction, ileo-psoas hematoma and knee hemarthrosis. Non-consanguineous parents, without altered paraclinical related family history. Performing complete F5 gene NGS + CNV sequencing for phenotype- endotype -genotype correlation. Results A probably pathogenic variant was identified, homozygous gene F5, consisting of the deletion of the thymine nucleotide at position 2.809 of the cDNA exon 13, (c.2809del) that at the protein level produces a frameshift change that leads to a premature stop codon. at amino acid 958 (p.Ser 937ValfsTer22) in a protein of 2224 amino acids. Discussion – Conclusion It is a single nucleotide deletion that occurs within the coding sequence of the F5 gene, leading to a frameshift variant. Which results in a non-functional truncated protein due to loss of critical C-terminal amino acid sequences. This variant is not reported in the databases HGMD-ClinVar-LOVD-dbSNP-gnomADv.4 - InternationalSocietyonThrombosisandhemostasismutation - InternationalRegistryofRBDsinMilan -theFVMutation. In silico predictors (autoPVS1yMutationTaster) report as deleterious. Artificial intelligence assistants (GenAI-VarChat-Alphafold-Mastermind) the variant was not reported, but was related to pathogenicity. Uniprot, Alliance of Genome Resources, BioCyc, MetaCyc-G66-30677, RefSeq, Ensembl, gene interaction networks and according to interpretation standards it is classified as pathogenic IA: PM1-PS1-PVS1-PM2. HPO, NCBIGene:2153 relate other phenotypes: Thrombophilia due to deficiency deficiency of activated protein C cofactor (AD); Budd -Chiari syndrome (AR); pregnancy loss recurrent (AD), Ischemic stroke (multifactorial). The genotypic and phenotypic heterogeneity of the gene, the presence of new and de novo variants as the case requires genomic, bioinformatics, algorithms, molecular, ontological studies, and artificial intelligence for specific diagnosis and treatment, correlation, monitoring, genetic counseling, generate knowledge in fields of medicine 7P.