Genomic Mutation Consequence Calculator

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Single Mutation Consequence Calculation -- FAQ -- Examples

*batch mode below*

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Genomic Assembly Version :: [ hg17(build35) and hg18(build 36.1) are both available]	hg17 May 2004 -- Build35 hg18 March 2006 -- Build36.1
Chrm::	chr1 chr2 chr3 chr4 chr5 chr6 chr7 chr8 chr9 chr10 chr11 chr12 chr13 chr14 chr15 chr16 chr17 chr18 chr19 chr20 chr21 chr22 chrX chrY chrM chr1_random chr2_random chr3_random chr4_random chr5_random chr7_random chr8_random chr9_random chr12_random chr15_random chr16_random chr17_random chr19_random chr22_random chrX_random chr6_hla_hap1 chr6_hla_hap2
Position::
Type::	Point Deletion *see indel caveat below Insertion *see indel caveat below
Reference Base :: [use an 'x' if this is unknown]
Mutation :: [string of bases for point/insertion, or # for Deletion]








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Batch Mutation Consequence Calculation -- FAQ

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Upload a CSV file in the following format::::
Mutation ID,Chromosome(format=chr# or chrX|Y),Position,Type(format=point,ins,del),Reference Base,Mutation*,AssemblyID[1=hg17,2=hg18].
*Mutation entries vary by 'type'. Point mutation entries expect a single base substitution. Ins entries expect a string of bases. Del entries expect a # of deleted bases.
ALSO- all reference and mutation bases are expected to be entered in + strand genomic context.
You will receive back a spreadshet of the full results keyed by the ID you specify. Use the ID you specify to merge results back into your data.


File Name:





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NOTES


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• Point mutations must only have a single base specified in Mutation
• Insertions must have 2+ bases specified in Mutation
• Deletions must specify the number of deleted bases in the Mutation field.
• All positions MUST be relative to the Human Genome build specified!
• To cite this tool, please use this Bioinformatics application note.




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Bugs / Questions

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• If you have any comments / questions / or bugs to report, please email the author at: major@cbio.msk.org



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Examples of MCC Results. **turn on 'old known gene' track in UCSC if viewing results in the UCSC browser.

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• EGFR - non-synonymous mutation effect on 1 isoform of EGFR. hg18 chr7:55227008 C->A .
• MAPK - mutation effects on 4 isoforms with two different non-synonymous effects! .hg18 chr5:179596124 C->A .
• CHEK2 - mutation effects on 9 isoforms with both non-syn, UTR, and intronic effects. chr22:27422945 C->A.
  



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General Information FAQ

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• What to the report column headings mean?

  --Summary Report--
    Symbol(ID): Gene Symbol (UCSC gene isoform ID)
    TX Exon: Transcribed exon number- includes UTR and CDS sequences.
    Description: Gene description
    Characterization: Displays the reference and mutant codon, makes a synonymous vs. non-syn call.
    Known SNP?: Is there a known SNP from DBSNP(build 126)
    Interpro Domains: Interpro domain spanning the specified region.
    S/P Disease Assoc: Swissprot Disease association information for this gene.
    S/P Reactome: SwissProt Reactome information for this gene.
    COSMIC Hits: Number, and details(in expanded view) of any COSMIC mutations known to span this position (build 34).
  
  --Expanded Coding & UTR Report--
  *All of the above fields
    Strand: + or - genomic strand.
    multiz17 Conservation Score: Conservation score from the UCSC conservation multiz17 track.
    TX Exon #: Transcribed exon number- includes UTR and CDS sequences.
    TX Exon Pos: Transcribed exon position- includes UTR and CDS sequences.
    Protein ID: Protein sequence ID
    mRNA Pos: Position of mutation in mRNA which still contains UTR.
    CDS Exon #: The coding sequence exon number.  This May differ from the TX exon number!
    CDS Pos:  Position in the coding sequence the mutation starts.
    AA Pos:  The amino acid position in the translated product.
    Ref Codon: The reference sequence codon.
    Mut Codon: The mutated codon.
    Synonymous/Non-Synonymous: Is the effect on the reference codon synonymous or nonsynonymous.
    Truncation: The CDNA position of the truncation, if any.
    Elongation: True or False for if the effect is a elongation.
    
  
  --Batch Mode Text Report--
  *All of the above fields
  User Specified ID:  THis is the ID (unique!) which the user assigns to each mutation being annotated.  The results include 
                      this ID so the user may join the results with the original mutation information. 
  
  
  

• How to interpret results?

  This will largely depend on your research goals.  
  The GMCC is meant as a tool to facilitate time consuming characterization and annotation of genomic mutations.  
  In single query mode, you can glean the information you need from the web reports-  which can be determining which 
  gene isoforms are affected by a mutation, if your mutation is synonymous or non-synonymous, if there are known SNPS or 
  COSMIC hits at this potition, or any other of the annotaions returned by GMCC.
  
  In the batch mode, the user will want to make sure all of her mutations have been assigned user specified unique IDS.  
  The text report file returned to the user will include these IDs which can then be used to merge the GMCC report 
  with the users data.
  
  * WARNING REGARDING INDELS *
  This tool is built with transcribed exons in mind.  When indels extend beyond an exon boundary, the results can be misleading.
  Always double check your indel results...
  





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MCC Single Mode FAQ

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• S1: What information is returned via the UI?
  the MCC will return the following for a given genomic mutation:

  Genomic Details:
    If the position has known SNPs, report those.
    Conservation Score (from multiz17 track)  **Only available for hg18
    Link to UCSC genome browser  **only in single mode
  
  Intergenic Hits:
    Any genes with downstream TXstarts within 50Kb, or upstream TXends w/in 50Kb.
    Gene details (name, symbol, description).
    Distance to TXstart.
  
  Intronic Hits:
    Gene details (name, symbol, description)
    Intron # 
  
  Splice Site Hits:
    Distance to exon boundary.
    TxExon #.
    Gene details (name, symbol, description)
    SwissProt disease and reactome association info.
  
  UTR Hits:
     Gene details(name, sym,desc)
     Tx exon #
     Tx exon position
     CDS exon # (if applicable)
     mRNA position
     SwissProt disease and reactome association info.
     ProteinID
  
  Coding Hits (for ALL splice variants involved at the specified position)
      All UTR info above.
      AA Position.
      Coding effect (reference and mutant codon and AA changes from reference... synonymous / non-synonymous call)
      Truncation position.
      Elongation end position(if it can be determined).
      Interpro Domain info.
      COSMIC info.
  
  *Pending:
    Transfac features. 

  
  
• S2: What source data supports this tool?
  The Postgres database which backs this tool is populated with information extracted from the UCSC Genome Browser. Some tables are used directly from UCSC, others are re-formatted to allow faster queries. The COSMIC data has also been included. The basic GMCC schmea can be obtained here.
  
  
  
• S3: How frequent will the updates be?
  The hg17 data will not be updated, the hg17 data was last updated on Oct 1 2006. The hg18 tables will be updated at a minimum twice per year, or as needed. The most recent update was completed on Feb 1 2007.
  
  
  
• S4: URL hacking?
  If you wish to run multiple mutations through this tool, please use the batch mode interface.
  
  
  
• S4: Which UCSC tables support the gene isoform results?
  When a mutation has an effect on multiple gene isoforms (and more rarely, multiple genes), the source data for these genes comes from the UCSC known genes track. UCSC attempts to merge several gene databases into a single group. This is largely successful, but there are rare cases where genes in Refseq or UniProt do not make it into the known gene set. These gaps should grow smaller and smaller with future updates.



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MCC Batch Mode FAQ

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*Please read all of the Single Mode FAQ as well, the info there applies to the Batch mode as well.


• B1: What information is returned via the Batch mode?
  All of the information from S1 above, minus any links to external resources. The data is returned in a single tab delimited file. Each distinct mutation may have multiple entries in the spreadsheet if it effects multiple splice variants or appears in several categories (ie. hits CDS in a gene, and also is upstream of another gene).
  
  
• B2: How many mutations can I process in batch mode?
  The software can generally process a single mutation in 0.5 to 2 seconds. You can process 10,000 mutations in roughly 4 hours. Please try to keep batch requests under 10,000 per session. If you have a very large number (> 100,000) to process, you can contact us directly, and we can arrange to run the software locally and return the results to you.