A lovely anonymous poster on the FORCE Message Boards gave a fabulous description of my genetic mutation. He/she put if very simply in laymen's terms.
My mutation is EX19DEL (aka c.8332-?_8488+?del)
My mutation is EX19DEL (aka c.8332-?_8488+?del)
All these weird question marks in the mutation name are a hallmark of the HGVS (Human Genome Variation Society) naming rules for big deletions / rearrangements.
All the lab typically knows is that a certain exon (or sometimes several of them) have been moved out of its proper place.
The easiest way to think about the exons is to imagine a novel published in a magazine, a chapter in every issue. If you have a stack of magazine and want to read the whole story, you read a chapter, skip a bunch of pages after it, pick the next issue, skip some pages before the next part of the story, and read on.
If it was a gene rather than a novel, then the in-between text you skip would be called an "intervening sequence", or intron. And the chapter you read would be called an exon.
Now suppose a chapter is missing. Maybe the whole magazine issue is lost, or maybe somebody ripped out a bunch of pages. Either way you don't have the whole story. Just how many "intron" pages are missing along with it wouldn't really matter for the reader.
But the HGVS rules demand that the lab reports the exact position of the lost part, to a letter, exon and intron alike. So a report would have to say something likec.8332-?_8488+?del
which means that the loss is from the "letter" 8332 in the story, to letter 8488, and they also miss an unknown number of "intron" letters before the "exon" chapter (that's minus-question mark), and an unknown number of letter after the exon (that's plus-question mark).
This kind of notation would typically draw a blank stare from a geneticist, of course. Are they, like, supposed to memorize where a letter 8332 is located in the story? So thankfully, the lab might explain the numeric mumbo-jumbo it in more transparent terms. Like, "it means that the exon number 19 is gone".
Mutations of this type are known as "large deletions" or "rearrangements". These "rearrangements" are not common. To make the matters worse, the traditional sequencing tests typically missed them. New, more sensitive tests have only become available recently.
Guess I was lucky. By the sounds of this, my mutation wouldn't have been found a few years ago!
and, the following was originally posted April 12, 2008
Everything you ever wanted to know about BRCA2 but were afraid to ask!
I have a deletion of Exon 19 on my BRCA2 gene, which means there's a tiny bit "missing" for lack of a better term. This throws off the genetic sequencing and the functionality of the gene.
Those of you who know me, know I'm a bit or a "researcher". I hunt and hunt until I find the information I'm looking for. In high school, I was also a bit of a wiz in biology, and especially genetics. This has helped me greatly trying to understand what being BRCA2 positive actually means. Below you will find some information that I hope will make sense...it certainly helped me understand everything. Some of it is pretty scientific, but after doing my researching, it's all fallen into place and I kind of understand it now.
Happy reading!!!
What is the BRCA2 gene?
The official name of this gene is “breast cancer 2, early onset.” BRCA2 is the gene's official symbol.
The BRCA2 gene belongs to a class of genes known as tumor suppressor genes. Like many other tumor suppressors, the protein produced from the BRCA2 gene helps prevent cells from growing and dividing too rapidly or in an uncontrolled way.
The BRCA2 gene provides instructions for making a protein that is directly involved in the repair of damaged DNA. In the nucleus of many types of normal cells, the BRCA2 protein interacts with several other proteins, including the proteins produced from the RAD51 and PALB2 genes, to mend breaks in DNA. These breaks can be caused by natural and medical radiation or other environmental exposures, and also occur when chromosomes exchange genetic material in preparation for cell division. By helping repair DNA, BRCA2 plays a role in maintaining the stability of a cell's genetic information.
Where is the BRCA2 gene located?The BRCA2 gene is located on the long (q) arm of chromosome 13 at position 12.3. More precisely, the BRCA2 gene is located from base pair 31,787,616 to base pair 31,871,804 on chromosome 13. The BRCA2 gene's location is indicated by the yellow arrow.
How are changes in the BRCA2 gene related to health conditions?breast cancer - increased risk from variations of the BRCA2 geneResearchers have identified more than 800 mutations in the BRCA2 gene, many of which are associated with an increased risk of breast cancer. Many BRCA2 mutations insert or delete a small number of DNA building blocks (nucleotides) in the gene. Most of these genetic changes disrupt protein production from one copy of the gene in each cell, resulting in an abnormally small, nonfunctional version of the BRCA2 protein. Researchers believe that the defective BRCA2 protein is unable to help repair damaged DNA or fix mutations that occur in other genes. As these defects accumulate, they can allow cells to grow and divide uncontrollably and form a tumor.
other cancers - increased risk from variations of the BRCA2 gene
In addition to female breast cancer, mutations in one copy of the BRCA2 gene can lead to an increased risk of ovarian cancer, prostate cancer, pancreatic cancer, fallopian tube cancer, male breast cancer, and an aggressive form of skin cancer called melanoma. Mutations in the central part of the gene have been associated with a higher risk of ovarian cancer and a lower risk of prostate cancer than mutations in other parts of the gene.What is Chromosome 13?Humans normally have 46 chromosomes in each cell, divided into 23 pairs. Two copies of chromosome 13, one copy inherited from each parent, form one of the pairs. Chromosome 13 spans about 114 million base pairs (the building blocks of DNA) and represents between 3.5 percent and 4 percent of the total DNA in cells.
Exon(s) DefinitionCoding sequence of DNA present in mature messenger RNA; DNA initially transcribed to messenger RNA consists of coding sequences (exons) and non-coding sequences (introns or "junk DNA"). Introns are spliced out of the messenger RNA prior to translation, leaving only the exons to ultimately encode the amino acid product. Introns have no apparent function.
BRCA2 has 27 Exons. I am missing Exon 19, which is somewhere central on the gene. I wasn't too thrilled to learn that mutations in the central part of the gene have a higher risk of developing ovarian cancer.
Deletion Definition A mutation in which one or more (sequential) nucleotides is lost by the genome. If the number lost is not divisible by 3 and is in a coding region, the result is a frameshift mutation. A frameshift mutation is a genetic mutation where part of the genetic code is removed from a chromosome and lost forever. This affects the overall genetic sequence, and the result can range from insignificant to fatal. This is what I have.
How my Exon 19 deletion would look:
Wild-type in genetics refers to typical or normal and Mutant means differing from the Wild-type; a mutation.
My genetic mutation according to the report I received from Cancer Genetics at the London Regional Cancer Program. The testing was done by Molecular Diagnostic Laboratory of the London Health Sciences Centre.
Genotype: BRCA2:EX19del
Comments: aka BRCA2: c.8332-?_8488+?19
Genotype: BRCA2:EX19del
Comments: aka BRCA2: c.8332-?_8488+?19
I have a deletion of Exon 19 on my BRCA2 gene, which means there's a tiny bit "missing" for lack of a better term. This throws off the genetic sequencing and the functionality of the gene.
Those of you who know me, know I'm a bit or a "researcher". I hunt and hunt until I find the information I'm looking for. In high school, I was also a bit of a wiz in biology, and especially genetics. This has helped me greatly trying to understand what being BRCA2 positive actually means. Below you will find some information that I hope will make sense...it certainly helped me understand everything. Some of it is pretty scientific, but after doing my researching, it's all fallen into place and I kind of understand it now.
Happy reading!!!
What is the BRCA2 gene?
The official name of this gene is “breast cancer 2, early onset.” BRCA2 is the gene's official symbol.
The BRCA2 gene belongs to a class of genes known as tumor suppressor genes. Like many other tumor suppressors, the protein produced from the BRCA2 gene helps prevent cells from growing and dividing too rapidly or in an uncontrolled way.
The BRCA2 gene provides instructions for making a protein that is directly involved in the repair of damaged DNA. In the nucleus of many types of normal cells, the BRCA2 protein interacts with several other proteins, including the proteins produced from the RAD51 and PALB2 genes, to mend breaks in DNA. These breaks can be caused by natural and medical radiation or other environmental exposures, and also occur when chromosomes exchange genetic material in preparation for cell division. By helping repair DNA, BRCA2 plays a role in maintaining the stability of a cell's genetic information.
Where is the BRCA2 gene located?The BRCA2 gene is located on the long (q) arm of chromosome 13 at position 12.3. More precisely, the BRCA2 gene is located from base pair 31,787,616 to base pair 31,871,804 on chromosome 13. The BRCA2 gene's location is indicated by the yellow arrow.
How are changes in the BRCA2 gene related to health conditions?breast cancer - increased risk from variations of the BRCA2 geneResearchers have identified more than 800 mutations in the BRCA2 gene, many of which are associated with an increased risk of breast cancer. Many BRCA2 mutations insert or delete a small number of DNA building blocks (nucleotides) in the gene. Most of these genetic changes disrupt protein production from one copy of the gene in each cell, resulting in an abnormally small, nonfunctional version of the BRCA2 protein. Researchers believe that the defective BRCA2 protein is unable to help repair damaged DNA or fix mutations that occur in other genes. As these defects accumulate, they can allow cells to grow and divide uncontrollably and form a tumor.
other cancers - increased risk from variations of the BRCA2 gene
In addition to female breast cancer, mutations in one copy of the BRCA2 gene can lead to an increased risk of ovarian cancer, prostate cancer, pancreatic cancer, fallopian tube cancer, male breast cancer, and an aggressive form of skin cancer called melanoma. Mutations in the central part of the gene have been associated with a higher risk of ovarian cancer and a lower risk of prostate cancer than mutations in other parts of the gene.What is Chromosome 13?Humans normally have 46 chromosomes in each cell, divided into 23 pairs. Two copies of chromosome 13, one copy inherited from each parent, form one of the pairs. Chromosome 13 spans about 114 million base pairs (the building blocks of DNA) and represents between 3.5 percent and 4 percent of the total DNA in cells.
Identifying genes on each chromosome is an active area of genetic research. Because researchers use different approaches to predict the number of genes on each chromosome, the estimated number of genes varies. Chromosome 13 likely contains between 300 and 700 genes. Genes on chromosome 13 are among the estimated 20,000 to 25,000 total genes in the human genome.
Exon(s) DefinitionCoding sequence of DNA present in mature messenger RNA; DNA initially transcribed to messenger RNA consists of coding sequences (exons) and non-coding sequences (introns or "junk DNA"). Introns are spliced out of the messenger RNA prior to translation, leaving only the exons to ultimately encode the amino acid product. Introns have no apparent function.
BRCA2 has 27 Exons. I am missing Exon 19, which is somewhere central on the gene. I wasn't too thrilled to learn that mutations in the central part of the gene have a higher risk of developing ovarian cancer.
Deletion Definition A mutation in which one or more (sequential) nucleotides is lost by the genome. If the number lost is not divisible by 3 and is in a coding region, the result is a frameshift mutation. A frameshift mutation is a genetic mutation where part of the genetic code is removed from a chromosome and lost forever. This affects the overall genetic sequence, and the result can range from insignificant to fatal. This is what I have.
How my Exon 19 deletion would look:
Wild-type in genetics refers to typical or normal and Mutant means differing from the Wild-type; a mutation.
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