Hi sanbar! I too have the BRCA2 result of "unknown significance". I am being treated as if it came back negative. Mainly because I am triple negative and we usually (but not always) fall into the BRCA1 category if we test positive. It basically means that there is a genetic difference on the particular DNA that is tested for BRCA2. The difference may or may not have anything to do with cancer. My onc. told me the lab will continue to test your difference (there are more than likely others who have the same variant). If they ever find a correlation to your particular variant causing cancer they will notify your doctor. My onc. has never seen this happen while he's been in practice (about 25 years). It really stinks because we will probably never find out if our particular variants caused our cancer. Wish I could tell you more. I hope this helps a little!

Sanbar, the GCs almost always tell to treat "uncertain variants" as negative, because most of the uncertain variants turn out to be benign later, when more information is gathered about them. There is a lot of poorly studied genetic variation in our DNA, and most of it is just fine. But the geneticists need a proof in each specific case, and takes time to collect the data.

 Some doctors may be inclined to treat a "particular" uncertain variant as dangerous, but only because they already know something special about that particular variant. Like maybe it tracked with cancer in families, or some research papers saidthat it may disrupt the normal function of the gene ... something of this sort. But one needs to research a specific variant, by its specific name, to figure it out. Not "an uncertain variant" but "the specific variant you got".

 I see that you already took part in research, through the testing in the family. Had your cancer-free mother been positive, you'd be more convinced that "your" variant doesn't cause cancer. But since she was negative, the family testing research didn't really yield useful data...

A regular Genetic Counselor would have a fit if told that a surgeon or an oncologist suggested BM or prophy ooph surgeries just because a patient without any family history had "an uncertain variant".

The genetic lab's report with an uncertain variant says in no uncertain terms (sorry for the pun), "ignore this genetic test result, rely on family history instead". So ignoring the family history instead, that's flying in the face of it.

BTW there is another recent thread on the same topic:

http://community.breastcancer.org/forum/112/topic/760321 

JT3 --- This is I think a relevant, recently published journal article about BRCA2 variants of unknown significance. I posted it in the "clinical trials, research news, podcasts, study results" forum a little while ago. I had trouble posting the link to the original article. If you use the link http://www.cell.com/ajhg/current and put in "BRCA 2" in the search engine you will get to it.

"Research test identifies BRCA2 gene mutations that lead to breast, ovarian cancers"

https://medicalxpress.com/news/2018-01-brca2-gene-...

http://www.cell.com/ajhg/fulltext/S0002-9297(17)30502-5

Volume 102, Issue 2, p233–248, 1 February 2018ARTICLE

Assessment of the Clinical Relevance of BRCA2 Missense Variants by Functional and Computational Approaches

"Up until now, it has only been possible to establish that 13 inherited mutations in BRCA2 are pathogenic and known to cause cancer," says Dr. Couch. "In this study, we identified 54 that increase the risk of cancer. Similarly, 21 known neutral mutations that do not increase risk of cancer can now be expanded to 73. These findings may help patients and their health care providers make better decisions about how to deal with information obtained through genetic testing."

"In their study, Dr. Couch and his co-authors describe a laboratory-based test that can establish which inherited mutations called variations of uncertain significance in the BRCA2 gene are involved in cancer."

https://community.breastcancer.org/forum/73/topics...

I'm 58. My GO recommended I remove my ovaries. I don't need them anymore and in her experience VUS patients develop ovarian cancer. I'm considered high risk since I'vealready had a cancer. I'm having the surgery this summer.