BRCA1 rs80358525: Understanding the 185delAG Founder Mutation
The rs80358525 variant, commonly known as 185delAG, is a pathogenic mutation in the BRCA1 gene. It is recognized as a founder mutation significantly associated with an increased risk of developing breast and ovarian cancer.
What each genotype means
Typical BRCA1 gene sequence
This genotype represents the standard, non-mutated sequence at this specific location in the BRCA1 gene. It does not carry the 185delAG founder mutation associated with increased hereditary cancer risk in certain populations.
This is the most common genotype found in the vast majority of the global population.
Increased hereditary cancer risk
This genotype indicates you carry one copy of the 185delAG mutation, a well-documented pathogenic variant in the BRCA1 gene. Research indicates that individuals with this mutation have a significantly higher statistical risk of developing breast and ovarian cancer compared to the general population.
This mutation is found in approximately 1% of individuals with Ashkenazi Jewish ancestry, making it a significant founder mutation in that population.
High hereditary cancer risk
This genotype indicates you carry two copies of the 185delAG mutation. This is an extremely rare condition that is associated with a very high risk of early-onset breast and ovarian cancer, and it may have implications for Fanconi anemia-like clinical presentations.
This homozygous genotype is exceptionally rare and is not typically observed in the general population.
What is the rs80358525 Variant?
The variant rs80358525, frequently referred to in scientific literature as 185delAG, is a specific genetic alteration located within the BRCA1 gene. Technically, this mutation involves the deletion of two nucleotides, adenine and guanine, at positions 68 and 69 of the coding sequence. Because this deletion occurs in the coding region, it causes a frameshift, which disrupts the normal reading frame of the genetic code. This disruption typically leads to the production of a truncated, non-functional protein. As a founder mutation, it is passed down through generations within specific ancestral groups, meaning that individuals who carry this variant often share a common distant ancestor. It is one of the most extensively studied variants in human genetics due to its clear clinical significance and its prevalence in specific populations.
The Role of the BRCA1 Gene
The BRCA1 gene provides instructions for making a protein that acts as a tumor suppressor. Under normal conditions, the BRCA1 protein plays a critical role in maintaining genomic stability by repairing damaged DNA. When DNA strands break, the BRCA1 protein helps coordinate the repair process, ensuring that genetic information is accurately copied during cell division. When a pathogenic mutation like 185delAG occurs, the cell's ability to repair DNA is significantly impaired. This loss of function can lead to the accumulation of further genetic errors, which may eventually cause cells to grow and divide uncontrollably. This mechanism is why mutations in this gene are strongly linked to an increased susceptibility to certain types of cancer, particularly those affecting the breast and ovaries, where the gene's repair functions are vital for maintaining cellular health.
Research and Clinical Significance
Research has consistently identified rs80358525 as a high-penetrance pathogenic variant. Studies have shown that individuals who inherit this mutation face a substantially higher lifetime risk of developing breast and ovarian cancer compared to the general population. The evidence for this association is considered strong, supported by decades of clinical data and molecular studies. For example, research indicates that this mutation is present in a significant percentage of Ashkenazi women diagnosed with early-onset breast or ovarian cancer. While the presence of the mutation does not guarantee that an individual will develop cancer, it indicates a significantly elevated risk profile. Because of this, clinical guidelines often recommend that carriers of this variant engage in specialized screening and risk-reduction strategies, which should always be discussed with a qualified healthcare provider or genetic counselor.
Population Frequency
The rs80358525 variant is notably more common in individuals of Ashkenazi Jewish ancestry than in the general population. While the prevalence of pathogenic BRCA1 variants in the general population is estimated to be between 1 in 300 and 1 in 800, the frequency of this specific founder mutation among Ashkenazi Jewish individuals is approximately 1%. This means that roughly 1 in 100 people in this population may carry the variant. Because it is a founder mutation, it is also found in other populations, though at much lower frequencies. The high prevalence in the Ashkenazi community is attributed to historical population bottlenecks and the founder effect, where a small group of ancestors passed the variant down to a larger number of descendants. Genetic testing for this specific variant is often included in panels for individuals with Ashkenazi heritage who have a family history of cancer.
Navigating Genetic Information
Understanding your genetic status regarding rs80358525 can be a powerful tool for personal health management, but it must be approached with care. If you are concerned about your risk, the most important step is to consult with a medical professional or a certified genetic counselor. They can help interpret your results in the context of your personal and family medical history. It is important to remember that genetic testing is not a diagnosis of cancer; rather, it is a measure of risk. If you carry this variant, your doctor may suggest more frequent screenings or other preventive measures tailored to your specific situation. Conversely, if you do not carry this variant, it does not mean you have no risk of cancer, as many other factors, including lifestyle and other genetic markers, contribute to overall health. Always rely on clinical guidance rather than self-interpretation of genetic data.
How common is this variant?
The rs80358525 variant is found in approximately 1% of individuals with Ashkenazi Jewish ancestry, making it a significant founder mutation in that population.
Frequently asked questions
What does it mean to be a carrier of the 185delAG mutation?
Being a carrier means you have one copy of the mutated BRCA1 gene. This increases your lifetime risk of developing breast and ovarian cancer compared to the general population.
Is the 185delAG mutation only found in Ashkenazi Jewish people?
No, while it is most common in the Ashkenazi Jewish population, it can be found in other groups. However, it is significantly rarer outside of this specific ancestral background.
Does having this mutation mean I will definitely get cancer?
No, having the mutation does not mean you will definitely develop cancer. It indicates a higher statistical risk, which allows for proactive health management and increased screening.
Should I get tested for the BRCA1 185delAG variant?
You should discuss genetic testing with your doctor or a genetic counselor. They can evaluate your family history and personal health to determine if testing is appropriate for you.
Sources & further reading
Educational information only, last refreshed 10/9/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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