BRCA 2 Variant of uncertain significance

There is a lot of normal genetic variation in these genes. Little changes which don't make it better or worse. There are also mutations which break the gene and increase the risk of cancer. And there are variants of unknown significance. They don't seem to be mutations, they don't damage the gene in any known way, but at the moment there is no proof if a particular uncertain variant is really benign. A few of these variants actually turn out to be dangerous.

 "Uncertain" doesn't mean that absolutely nothing is known about each particular variant. Some variants already have a clue here or there, just not enough to solve the riddle for good yet. Some people search for these clues for their specific variants. Others just ignore the uncertain variants and go on knowing that the test wasn't informative. Probably negative but no 100% guarantee yet.

I had a similar result on BRCA1- "first observation" meaning this variant had NEVER been seen before. Aren't I special! My father was then tested and he had the same variant. He had 3 bouts with cancer: colon, bladder and leukemia which he died from at age 83.

My oncologist was reassuring and I also discussed questions with a specialist at Myriad. The only breast cancer in my family is my first cousin on my mother's side. My oncologist says my brother should be tested and that my cousin should be tested for further information. I haven't wanted to bring it up with them though- implications are for my other breast (prophylactic MX?) my children, my brother's children and my cousin's sisters, and they may NOT want to know or worry about this. Hard to know whether or how to pursue it.

But Since it could be beneficial for me and my children I think I should bring it up. 

Hi Warrior 3,

My test results came back that I have a "variant"  of which only 11 other people have (of everyone that's been tested). It sounds like you are one of the 11 others. My doctors said they don't think it is like a "positive"  result. They will be following us to see who if any develop BC. That's my understanding of it. I used that info when I decided to have a unilateral instead of bilateral mx. It seems the variant is more like a negative result for the gene.

Kim

I just got my results today....

everything was No Mutation Detected except in BRCA2 sequencing the results said Uncertain Significance.  Doctor still want me to have a hysterectomy but thinks I can leave my ovaries.  Both my mom and grandma had breast cancer so my risks are high already.  Your thoughts.........?

I did too came back positive with BRCA2 mutation after I got diagnosed with DCIS stage 0, my breast surgeon gave me the option of doing a lumpectomy with radiation or full mastectomy without radiation. But since BRCA 2 came back positive, which means nothing inconclusive, not enough data to support what it means. It may or may not be a risk factor for developing BC in my other breast. They said it is up to me to decide what I want to be done and they will totally support it. Luckily my insurance would cover for it. So I opted to have bilateral mastectomy with DIEP reconstruction. It is a big major surgery, took 11 hours in operating room. And guess what, my pathology showed I have micro-invasive ductal carcinoma. And if I did not have my other breast removed then, then that is the next step or have chemo and radiation. So now I just have to deal with concentrating in healing which is no picnic. I know everyone is different but my thoughts are then is out of sight, out of mind. I just don't want it in my body at all.

Hi Ginger_16, We just wanted to welcome you to Breastcancer.org, and let you know that we're so glad you've found our community

You may find articles on our main site breastcancer.org of interest, such as BRCA1 and BRCA2 Testing and others.

You may also find the FORCE website has a lot of information for you as they focus on hereditary breast and ovarian cancer.We hope this helps in your search for quality information.

The Mods

Each of the variants reported as uncertain is a different story. Some are virtually unknown, others have quite a bit of info from the studies. Some are extremely rare and others are known in dozens, sometimes even hundreds cases. Some are reported as uncertain by every lab, but for others, a reporting lab may be behind the curve when others have already figured it out.

So if you are looking for a better picture of your specific variant, then it makes relatively little sense to ask "in general" about all variants and all labs. Be more specific if you can.

It's a good thing you got help from the GC, Ginger. When a variant is rare, it's difficult for scientists to get enough data to give you a straight answer on it. At first, they might guess whether it's deleterious or not based on its location in the gene; some parts of the DNA "recipe" are more important than others. Over time (years), you can hope that they collect enough data to give you a better answer. Someone may do more research into the gene at the DNA level, or they can collect reports of cancer (or no cancer) from other people with the same mutation to see if cancer seems to be more common in people with the mutation or not.

Warrior3, if you can talk to a Genetics Counselor about this, it should help you too. If he or she thinks it's a good idea to get a test from another lab, you can hopefully get a single-site test, which is much less expensive. The GC can also help you file with your insurance. Ambry Genetics, for example, rarely charges you more than $100 out of pocket for a single-site test, and they'll even call you before charging you if they think the cost will be more than that.

My BRCA2 is IVS10+1G>A It is listed as "suspected deleterious"...Not sure what to do. My Dr. recommended BMX and ooph (I am not up on the abbreviations just yet I hope I got them right). I called Myriad and was told they treat it the same as deleterious but has not been seen as much as a deleterious. I am scheduled for an ooph next week (I will continue to monitor my breasts with mammo/MRI's) and a bit freaked out. Not positive that I won't chicken out.

I found a lump on my right breast 3 years ago, the biopsy was benign but they had me come every 6 months for mammo or sonogram. After 2 years I went for the last of my last 6 mos check ups and was looking forward to annuals when they found something in my other breast (no biopsy needed). They told me to come back in 6 mos. I saw a breast surgeon instead since I was worried. She did follow up sono and recommended genetic testing due to my family history (paternal aunt died of breast & ovarian cancer, 2 paternal 2nd cousins both had mastectomies). My test came back BRCA2 positive. Since then I have continued surveillance and during my last internal ultrasound (at cancer hospital) they found a polyp in my uterus. I had an MRI which was clear but I am afraid and tired of the roller coaster. I am scheduled for surgery to remove ovaries and fallopian tubes and was told that I can continue to monitor my breasts but ovarian cancer is very hard to detect. If I maintain 6 mos mammo/MRI they feel they will catch any malignancy early enough to treat with surgery/chemo. I am wondering if anyone else has had an ooph and what should I expect? I am trying to stay calm and to go through with it but having strong doubts...

First time here, and I'm a bit overwhelmed to see so many many people, and I think of all the loved ones and families behind each of these stories, it breaks my heart!

Not sure where to post, but this seems the most relevant topic. I am struggling with the decision whether to have surgery based on my genetic test.

I was referred for genetic testing following my breast cancer treatment because of my family history. I too have a BRCA2 variant of unknown signifance. I'm premenopausal and have developed a 4.7mm ovarian cyst of a year on Tamoxifen. I went last week for what I thought would be an appointment to discuss whether to remove the cyst (doc seems confident it's benign, but said the only way to be sure would be to remove it for examination). Instead, I ended up meeting with a gynaecological oncologist who advised me that my case of genetic testing had come up in the consultants' meeting. She advised me that they wanted to give me the option of having my ovaries and tubes removed, given the possibility that the Brca2 variant may mean an increased risk for ovarian cancer. This really surprised me,as it is so different from the advice given by the genetic counsellor months ago. However with the cyst problem as well, I am now thinking I should consider the surgery. I'm 44. I am done having kids, but not happy about facing early menopause.Then I also think - surely I must take this option as it may give me more time to be here for my children?

How are others following up with a variant of unknown significance

I'm tested positive for BRAC 2 and I'm trying to decide about having a prophylatic masectomy.

I am trying to decide on the same option . What did you decide to do Tany?