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
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