Diagnostic Analysis Framework

Please read and follow the latest guidelines from the Diagnostic Variant Analysis Pipeline Workflow

This diagnostic analysis framework has been developed to filter for and prioritize pathogenic variation/mutation in patient samples. Analysis can be done on trios or non-trios depending on the context.

Relevant reading material:
a) Xiaolin's 2015 manuscript nicely demonstrates the application of the IGM trio interpretation framework:
b) An introductory slide-set created to give a conceptual introduction to the framework and to give you an idea of the overall flow:

A list of the inheritance rules used by ATAV's trio interpretation pipeline can be found in the attached trio_rules.txt

Analysis Commands

Filtering Rules

For any questions or issues running the diagnostic analysis please contact Evan () or Joe ()

Publications that have involved the IGM Diagnostic Analysis Framework:


Shashi V, Pena LDM, Kim K, Burton B, et al. De novo truncating variants in ASXL2 are associated with a unique and recognizable clinical phenotype: further involvement of the ASXL gene family in neurodevelopmental genetic syndromes. American Journal of Human Genetics 2016; 6;99(4):991-999.

Kim J-H, Shinde DN, Reijnders MRF, Hauser NS, et al. De novo loss-of-function mutations in SON disrupt RNA-splicing of genes essential for brain development and metabolism, causing an intellectual disability syndrome. American Journal of Human Genetics 2016; pii: S0002-9297(16)30267-1.

Petrovski S, Parrott RE, Roberts JL, Huang H, et al. Dominant Splice Site Mutations in PIK3R1 Cause Hyper IgM Syndrome, Lymphadenopathy and Short Stature. Journal of Clinical Immunology 2016; 36(5):462-71.

Petrovski S, Küry S, Myers CT, Anyane-Yeboa K, et al. Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia and seizures. American Journal of Human Genetics 2016; 98 (5), 1001-1010.


Halvorsen M, Petrovski S, Shellhaas R, Tang Y, Crandall L, Goldstein DB, Devinsky O. Mosaic mutations in early-onset genetic diseases. Genetics in Medicine 2015; doi: 10.1038/gim.2015.155.

Williams C, Jiang YH, Shashi V, Crimian R, Schoch K, McHale D, Goldstein DB, Petrovski S. Additional Evidence that PGAP1 Complete Loss of Function Causes Autosomal Recessive Global Developmental Delay and Encephalopathy. Clinical Genetics 2015; doi: 10.1111/cge.12581

Petrovski S, Shashi V, Schoch K, Petrou S, et al. Exome sequencing results in successful riboflavin treatment of a rapidly progressive neurological condition. Molecular Case Studies 2015; doi:10.1101/mcs.a000257

Dobbs K, Conde CD, Zhang SY, Parolini S, et al. DOCK2 and recessive immunodeficiency with early-onset invasive invasive infections. New England Journal of Medicine 2015; 372(25):2409-22

Zhu X, Petrovski S, Xie P, Ruzzo EK, et al. Whole exome sequencing in undiagnosed genetic diseases: Interpreting 119 trios. Genetics in Medicine 2015; 17,774–781.


Shashi V, Xie P, Schoch K, Goldstein DB, et al. The RBMX gene as a candidate for the Shashi X-linked intellectual disability syndrome. Clinical Genetics 2014; doi: 10.1111/cge.12511

Need AC, Shashi V, Hitomi Y, Schoch K, Shianna KV, McDonald MT, Meisler MH, Goldstein DB. Clinical application of exome sequencing in undiagnosed genetic conditions. Journal of Medical Genetics 2012; doi:10.1136/jmedgenet-2012-100819