BRCA2 rs80357094: Understanding This Rare Genetic Variant
The rs80357094 variant is a rare genetic alteration located within the BRCA2 gene. It is recognized in clinical literature as a pathogenic variant associated with an increased risk of hereditary breast and ovarian cancer syndromes.
What each genotype means
Typical BRCA2 genotype
This genotype represents the common, non-variant sequence at this position in the BRCA2 gene. It is considered the expected baseline in the general population and is not associated with the increased hereditary cancer risks linked to the variant form.
This is the most common genotype found in the vast majority of the global population.
Potential hereditary cancer risk
This genotype indicates you carry one copy of the variant, also known as c.7879A>T or p.Ile2627Phe. Research has identified this variant in families with hereditary breast and ovarian cancer, and it is classified as likely pathogenic in clinical databases. Please discuss these findings with a genetic counselor or healthcare provider to understand your personal and family health context.
This specific variant is extremely rare and is not typically observed in large-scale general population databases.
Potential hereditary cancer risk
This genotype indicates you carry two copies of the variant, also known as c.7879A>T or p.Ile2627Phe. Because this variant is associated with hereditary breast and ovarian cancer risk, carrying two copies warrants a thorough discussion with a medical professional or genetic specialist regarding your clinical management. This result does not constitute a medical diagnosis.
This genotype is exceptionally rare and has not been documented as a common occurrence in human populations.
What is rs80357094?
The rs80357094 variant is a single nucleotide change in the BRCA2 gene, specifically identified as c.7879A>T, which results in the amino acid substitution p.Ile2627Phe. This variant is located within the DNA-binding domain (DBD) of the BRCA2 protein. The isoleucine residue at this position is highly conserved across species, meaning it has remained largely unchanged throughout evolutionary history. When this specific amino acid is replaced by phenylalanine, it can alter the protein's structure and function. Because this variant is found in the critical DNA-binding region, researchers have focused on how this change might disrupt the protein's ability to interact with DNA, which is essential for maintaining genomic stability.
The Role of the BRCA2 Gene
The BRCA2 gene provides instructions for making a protein that acts as a tumor suppressor. This protein plays a vital role in repairing damaged DNA, particularly through a process called homology-directed repair (HDR). By fixing double-strand breaks in DNA, the BRCA2 protein helps ensure that genetic information is accurately copied when cells divide. When the BRCA2 gene functions correctly, it prevents the accumulation of harmful mutations that could lead to uncontrolled cell growth. However, when a pathogenic variant is present, the BRCA2 protein may be unable to perform these repairs effectively. This loss of function can lead to genomic instability, which is a hallmark of cancer development, particularly in tissues such as the breast, ovaries, and prostate.
Research and Clinical Evidence
Clinical evidence for rs80357094 is categorized as pathogenic or likely pathogenic by multiple clinical laboratories. Research has demonstrated that this variant impairs the homology-directed repair activity of the BRCA2 protein. Furthermore, studies have shown that it affects the regulation of centrosome amplification and fails to complement the lethality in BRCA2-deficient cells. These functional assays provide strong evidence that the variant is deleterious. It has been reported in various families and individuals with a history of breast and ovarian cancer. Because of this, it is considered a significant contributor to hereditary cancer risk. The classification of such variants is often supported by the ACMG/AMP framework, which integrates functional data with clinical observations to determine the likelihood that a variant will cause disease.
Population Frequency
The rs80357094 variant is classified as rare. It is not typically found in large-scale population databases, such as the Genome Aggregation Database (gnomAD). In genetic research, the absence of a variant in the general population is often used as evidence to support its potential pathogenicity, as high-risk variants are generally not common in healthy, unselected populations. Because it is so rare, it is not a variant that would be expected in the general public. Its presence is usually identified through targeted clinical genetic testing in individuals or families who already have a strong personal or family history of specific cancers, rather than through routine population screening.
Managing Genetic Information
If you have received information about this variant, it is important to understand that genetic results are complex and should be interpreted by a qualified healthcare professional, such as a genetic counselor or a medical geneticist. A pathogenic variant in BRCA2 does not mean that a cancer diagnosis is inevitable; rather, it indicates an increased lifetime risk compared to the general population. This information can be used to guide personalized screening and risk-reduction strategies. You cannot change your genetic code, but you can use this knowledge to make informed decisions about your health. Always discuss your specific results, family history, and potential management options with your clinician. They can provide context based on your personal health profile and help you navigate the next steps in your medical care.
How common is this variant?
The rs80357094 variant is considered rare and is not typically observed in large-scale population databases.
Frequently asked questions
What does it mean if I have a BRCA2 variant?
A pathogenic BRCA2 variant indicates an increased risk for certain cancers, such as breast, ovarian, and prostate cancer. It does not mean you have cancer, but it suggests that your body's DNA repair mechanisms may be less efficient.
Is rs80357094 the same as other BRCA2 mutations?
No, every variant is unique. While rs80357094 is a specific change in the BRCA2 gene, other variants occur at different locations and may have different effects on protein function.
Should I get tested for this variant?
Genetic testing is usually recommended based on your personal or family history of cancer. You should consult with a genetic counselor to determine if testing is appropriate for your specific situation.
Can I fix a pathogenic BRCA2 variant?
Currently, there is no medical way to 'fix' or change a genetic variant in your DNA. Management focuses on increased cancer screening and risk-reduction strategies recommended by your doctor.
Sources & further reading
Educational information only, last refreshed 11/2/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This variant is a rare pathogenic mutation in the BRCA2 gene associated with hereditary breast and ovarian cancer syndrome.
This variant is a clinically significant allele in the BRCA2 gene associated with hereditary breast and ovarian cancer syndrome.
This variant (p.Lys3326Ter) is classified as a benign polymorphism and is not considered a primary driver of hereditary breast and ovarian cancer susceptibility.
A pathogenic variant in BRCA2 associated with hereditary breast and ovarian cancer syndrome.
A pathogenic variant in the BRCA2 gene associated with hereditary breast and ovarian cancer.
A rare pathogenic variant in the BRCA2 gene associated with hereditary breast and ovarian cancer syndrome.