Question-- how to use variant annotation integrator to represent a single or very few mutations?

[Sampson, Jacinda B.]

I would like to be able to use all the useful UCSC tools to visualize a single variant and its  SIFT, MutationTaster, etc scores. .  For example, I want to look at G93A mutation in SOD1, linked to ALS. Or, maybe, a short list to represent all the ALS SOD genes with their SIFT scores. 

How do I input that data? It would not be from a large file of  .vcf format.

Jacinda Sampson

[Jonathan Casper]

Hello Jacinda,

Thank you for your question about the Variant Annotation Integrator. While we are planning to develop a feature where you can provide variants in HGVS format, it is not ready yet. In order to enter your variants, you will need to identify the genomic locations and nucleotide changes. You can then paste these into pgSnp format (http://genome.ucsc.edu/FAQ/FAQformat.html#format10) and load them into the VAI tool that way. Alternatively, if you are able to obtain rs# IDs from dbSNP for your variants, one of our engineers has offered to set up a demo browser where you can pass those directly to the VAI tool. Many disease mutations will not be in dbSNP, but please let us know if you are interested in using this option for the ones that are. Instructions for constructing your own pgSnp file follow.

As stated above, to construct a file in pgSnp format you will need the genomic location and nucleotide changes for your variants of interest. For help obtaining the genomic position of variants in a number of ALS-related genes, you can use the following table: http://alsod.iop.kcl.ac.uk/misc/dataDownload.aspx#C1. Note in particular the columns "Mutation name", "HGVS_Nucleotide", and "Location(Chr)". The G93A variant of SOD1, for example, corresponds to a G>C nucleotide change at position chr21:33039612 in the GRCh37 human genome assembly. In pgSnp format, that variant is described as follows:

chr21 33039611 33039612 G/C 2 0,0 0,0

The two "0,0" entries are placeholders for allele frequency and quality scores. Note also that the start coordinate in pgSnp format is 33039611 - one less than the named position of the variant.

Write that pgSnp line into a plain text file along with other lines for any other variants of interest, and you can upload the file to the UCSC Genome Browser as a custom track. The Variant Annotation Integrator will then examine those variants when you choose "User Supplied Track" from the "Select Variants" menu.

Steps to load this file as a custom track into the VAI tool:
1. Open the Variant Annotation Integrator at http://genome.ucsc.edu/cgi-bin/hgVai
2. Click "Add custom tracks" 
3. Select Clade: Mammal, Organism: Human, Assembly: Feb. 2009 (GCRh37/hg19)
4. Click "Upload File" and select the file of pgSnp variants you have prepared
5. Click "Submit" 
6. Click "go to variant annotation integrator"

I hope this is helpful. If you have any further questions, please reply to gen...@soe.ucsc.edu. Questions sent to that address will be archived in a publicly-accessible forum for the benefit of other users. If your question contains sensitive data, you may send it instead to genom...@soe.ucsc.edu.

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Jonathan Casper
UCSC Genome Bioinformatics Group

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