Rearrangement Overview

This tab shows a table of breakpoints for the rearrangement

The accurate description and annotation of structural variants can be complex. 
This is due to the different resolution that variants are reported from traditional 
cytogenetic coordinates down to the actual base pair positions. Furthermore, multiple 
rearrangements in a single area of the genome can make cataloguing and interpreting 
their effects challenging. 

The Rearrangement Overview page describes the one or more breakpoints which make up a structural 
variant. A breakpoint is defined as a region or point where the sample sequence has altered
from the reference sequence. Minimum interpretation is made of this data. One variant event
can consist of one or multiple breakpoints. The Syntax (shown above the table) gives a detailed 
description of the variant and its location  (e.g. chr11:g.36585230_76606619del, a deletion of 
roughly 40Mb on chromosome 11). Syntax is based on HGVS mutation nomenclature recommendations
[http://www.hgvs.org/rec.html]. 

In the table of breakpoints, the columns are as follows:-

    Mutation ID (COST)         Unique identifier for the variant

    Mutation Description       A short textual description of the variant 
                               (e.g. tandem duplication, deletion, translocation)

    Order	               For a structural variant involving multiple breakpoints, 
                               the predicted order along chromosome(s) is given (otherwise '0').

    Chromosome From 	       Gives the chromosome where the first variant/breakpoint occurs.

    Breakpoint From            Genomic coordinate of the start of the variant/breakpoint 
                               (or range if base position not known). The icons next to the 
                               coordinate are links to the COSMIC Genome Browser and Ensembl.

    Strand 	       	       Orientation of the break relative to the reference sequence.

    Chromosome To 	       Gives the chromosome where the final variant/breakpoint occurs.

    Breakpoint To 	       Genomic coordinate of the last variant/breakpoint 
                               (or range if base position not known).
			       The icons next to the coordinate are links to the COSMIC Genome 
                               Browser and Ensembl.

    Strand 	       	       Orientation of the break relative to the reference sequence.

    Non Templated Inserted Seq Sequence (if any) which is inserted at the breakpoint. The sequence
                               is not encoded.


A controlled Ontology of "Mutation Descriptions" are available below. 

Mutation Description Ontology
In order to help with the interpretation of structural variants in COSMIC, each variant is assigned 
a Mutation Description and Syntax. When the assignment takes place there is an interpretation
of the data and the currently known breakpoints in the region. If not all breakpoints have been 
characterised then the mutation may not be fully characterised. Below is a description of the Mutation 
Description Ontology with associated Syntax.

  1. Tandem Duplication
     A Tandem Duplication is characterised by a duplication of a segment of the genome which is 
     adjacent to the original sequence. The syntax takes the following format:

        chr2:g.124629221_125036287dup 

     where chr2: denotes the chromosome involved, g. genomic coordinates used, 124629221_125036287 
     the start and end of the variant, dup indicates tandem duplication.

     For a tandem duplication the breakpoint is characterised by upstream sequence mapping 
     downstream to where it should map on the genome. So in this case position 125036287 is mapping 
     before 124629221 which is the signature of a tandem duplication. 

  2. Deletion
   The syntax takes the following format:

       chr11:g.36585231_76606618del

   where chr11: denotes 
   the chromosome involved g. for genomic coordinates, 36585231 for the deletion start point, 76606618 
   for deletion end point and del indicates a deletion event.

   For a deletion the breakpoint is characterised by 2 distant points in the genome being next to each 
   other. In this example position 36585230 is next to 76606619 in the genome. The region between these 
   points is assumed to be deleted. The coordinates of the deletion are +1 and -1 as the breakpoint gives 
   the last observed nucleotides, so the range of the deletion is from 36585231 to 76606618.

  3. Inversion
   An inversion indicates the reversal of a piece of genome sequence. The syntax takes the following 
   format:

       chr1:g.115340245_115346449inv 

   where chr1: denotes the chromosome involved g. genomic coordinates used, 115340245_115346449 the 
   range of the inversion, and inv indicates an inversion.

   Two breakpoints can be detected for this mutation although only one is required to fully characterise 
   the mutation. 

  4. Translocation
   A Translocation is characterised by the fusion of 2 chromosomes. The syntax takes the following format:
 
      chr8:g.63669858_chr14:22298219trans[?] 

   Where chr8:g.63669858 denotes the breakpoint on one chromosome, and chr14:22298219 on the other chromosome, 
   trans indicates a translocation event, [?] indicates if there is any change in copy number associated 
   with the mutation. [?] indicates not known. 

   The strand information is often given in the syntax to describe which end of each chromosome actually 
   forms the translocation.

  5. Complex Substitution
   A Complex Substitution is defined as a region which been deleted and replaced with another region of 
   the genome. The syntax takes the following format:

      chr8:g.55512043_63659930>chr13:22017510_22017585 

   where chr8: denotes the chromosome involved g. for genomic coordinates, 55512043_63659930 indicates the 
   region deleted, > represents replaced with, chr13:22017510_22017585 indicates the region inserted.

  6. Complex Amplicon
   A Complex Amplicon is a region of a genome which has been amplified and undergone multiple rearrangements. 
   Due to the complexity of these regions the amplicon breakpoints are listed but no interpretation is 
   made of the data.

   The syntax gives the range of the amplicon where the multiple rearrangements are occurring. 
   An example is 

      chr8:g.(61857345-?_129022677+?)[(10-40)] 

   where chr8: denotes the chromosome involved g. for genomic coordinates, 61857345-?_129022677+? 
   indicates the range of the amplicon with -? and +? indicating the precise position of the 
   start (-?) and end (+?) are not currently known, [(10-40)] indicates the approximate copy number 
   of this region, between 10 and 40 copies in this case. 

  7. Amplicon Breakpoint(s)
   An amplicon breakpoint is defined as a breakpoint within an amplified region with unknown boundaries 
   so accurate interpretation of the mutation cannot be made. In these cases the breakpoint is simply 
   described. The syntax takes the following format:

      chr14:g.28412748_chr14:28419493bkpt[4] 

   where chr14: denotes the chromosome involved g. for genomic coordinates, 28412748 is the end of the 
   sequence to the left of the breakpoint and 28419493 is the sequence coordinate to the right of the 
   breakpoint, bkpt indicates a breakpoint, and [4] the approximate copy number in the area.

Sequence Fragment(s)
Structural variants can have additional sequence from elsewhere in the genome.
For example:

    chr8:g.64123513inschr12:7418993_7419327inschr12:8232312_8232333_chr12:7072996trans[(8-13)] 

is a translocation with 2 additional fragments from chromosome 12, one is 21 base pairs and the 
other 335 base pairs.
   
Copy Number Information
Approximate Copy Number data is given when the variant is non-diploid and this information is available. 
The mutation description is prefixed with "amplified" or "amplicon" if there is variation in copy number. 
For example chr8:g.63669858_chr14:22298219trans[11-26] denotes a translocation with a copy number increase 
of approximately 11-26. A value of [2] would indicate diploid (normal).

Strand Information
In certain situations it is important to provide strand information to describe a variant. 
The HGVS "o" identifier is used to denote 'opposite strand'.

For example:

    chr1:g.58958334_chr12:o69893440bkpt

Rearrangement Overview - Samples

This tab shows the associated samples/tissues for the rearrangement

Help Index