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Improved accuracy of mitochondrial variant classification

By Charles Chapple on November, 16 2022

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Charles Chapple

Head of Bioinformatics

As part of our routine maintenance and updating of external data sources, we have now included gnomAD v3 frequencies for mitochondrial (MT) variants in analyses run against the hg19 reference genome. 

When aligning FASTQ data on VarSome Clinical against hg19, we use our modified hg19 reference genome which includes the standard mitochondrial reference sequence, the revised Cambridge Reference Sequence (rCRS), which is also the mitochondrial sequence found in the hg38 reference genome. This means that gnomAD hg38-based frequency data for mitochondrial variants are applicable to variants analyzed by VarSome Clinical against the hg19 reference genome, as our hg19 reference genome uses the same chromosome as in the hg38 reference genome.

Please note that when annotating user-provided VCF files, instead of FASTQ samples, with hg19, VarSome Clinical will use either NC_001807.4 (the default mitochondrial sequence in hg19) or the rCRS depending on whether a variant is given in the VCF as being on "chrM" or "MT", with "chrM" variants taken as referring to the NC_001807.4 sequence and "MT" variants as referring to the rCRS. For more details, please see here.

Because of this, we have included hg38 frequency data for MT (and not chrM) mitochondrial variants in analyses run from either FASTQ or VCF files on VarSome Clinical against either hg38 or hg19 reference genomes; and for individual look ups on VarSome.com.

Further Information and Support

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As ever we hope you find these changes and improvements helpful, we’d love to hear any suggestions you may have, support is available as usual from support@varsome.com

 

- The VarSome Team

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