Anna Abraham
Anna Abraham
Helios Scholar

School: Arizona State University
Hometown: Phoenix, Arizona
Mentored by: Keri Ramsey, R.N., C.C.R.N.

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Re-Analysis of Genomic Sequencing Data at the Center for Rare Childhood Disorders

TGen’s Center for Rare Childhood Disorders has enrolled over 600 patients for Whole Exome and Whole Genome Sequencing with a current diagnostic rate of about 40%. This means that, to date, over 350 families in the study remain undiagnosed. However, the study of genomics is a growing field and the genetic causes of new disorders are rapidly being discovered. Due to this increase in knowledge and advances in new sequencing technology, we expected that re-analyzing cold cases would result in a higher rate of success in finding the genetic causes of our patients’ disorders. In order to do this, new VarSeq files were created for 42 unsolved cases that were originally analyzed between the years of 2012-2019. VarSeq files are annotation files that narrow down the data to the variants that are most likely relevant to finding the cause of a patient’s symptoms. Databases such as OMIM, ClinVar, gnomAD, and PubMed contain the most updated discoveries and publications about genes and mutations. These databases were used to search for recent information that could connect a patient’s genotype to their phenotype (list of symptoms).  At the end of this re-analysis, we discovered the following: one pathogenic variant, one likely pathogenic variant, four variants of uncertain significance (VUS) that are associated with disease, 17 VUS that have not been previously associated with disease, and three incidental findings. This demonstrates that re-analyzing genomic data can increase diagnostic rates, uncover new variants of uncertain significance, and yield a higher number of incidental findings. With these new discoveries from re-analysis, families can not only receive a diagnosis, but can gather more information about their child’s disorder and connect with experts who are studying these rare diseases.