2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-How Does Multiomics Help Variant Reclassification?

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The study analyzed the reclassification of variants of uncertain significance (VOUS) in genes related to lysosomal storage disorders. The researchers found that biochemical results alone were insufficient for variant reclassification and that additional information from multiomics approaches is necessary. Multiomics refers to the integration of multiple omics technologies, such as genomics, transcriptomics, proteomics, and metabolomics, to gain a comprehensive understanding of biological systems.<br /><br />The researchers reclassified several variants from uncertain significance to disease-causing by incorporating RNA sequencing results or biochemical profiles with clinical phenotype and family history. They specifically investigated the biochemical and molecular results of three lysosomal storage disorders: Pompe, Fabry, and Gaucher disease.<br /><br />The study found correlations between certain variants and biochemical results in the GAA, GBA, and GLA genes. For example, in the GAA gene, variants were grouped based on enzyme activity levels. The study also provided demographic information on patients with these disorders.<br /><br />The conclusion of the study emphasizes the importance of multiomics approaches in variant reclassification. It states that additional information from multiple measurements, integrated analysis methods, and computational infrastructure is required to interpret VOUS variants accurately. The use of advanced omics technologies is also highlighted, as they can help discover additional biomarkers and enhance the understanding of the genotype-phenotype relationship. Accurate variant classification and interpretation through the incorporation of multiomics can aid in personalized genetic counseling and reduce unnecessary medical visits and family anxiety.<br /><br />Overall, the study demonstrates the significance of multiomics approaches in improving the early diagnosis and personalized treatment of lysosomal storage disorders.

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Presenting Author - Ruby Liu, PhD, CGC; Co-Author - Fen Guo, PhD, FACMG, FCCMG; Co-Author - Babi Ramesh Reddy Nallamilli, PhD; Co-Author - Christin D. Collins, PhD, FACMG; Co-Author - Lora H. Bean, PhD; Co-Author - Naga M. Guruju, PhD, FACMG; Co-Author - Madhuri Hegde, PhD;

Meta Tag

Genetic Testing

Lysosomal Diseases

NextGen Sequencing

Sequencing

Co-Author Fen Guo, PhD, FACMG, FCCMG

Co-Author Babi Ramesh Reddy Nallamilli, PhD

Co-Author Christin D. Collins, PhD, FACMG

Co-Author Lora H. Bean, PhD

Co-Author Naga M. Guruju, PhD, FACMG

Co-Author Madhuri Hegde, PhD

Presenting Author Ruby Liu, PhD, CGC

Keywords

reclassification

variants of uncertain significance

genes

lysosomal storage disorders

biochemical results

multiomics approaches

genomics

transcriptomics

proteomics

metabolomics