BRCA2 rs397509279: Understanding This Rare Genetic Variant
The rs397509279 variant is a rare genetic alteration located within the BRCA2 gene. It is classified as a pathogenic or likely pathogenic variant associated with hereditary breast and ovarian cancer syndrome.
What each genotype means
Typical BRCA2 genotype
This genotype represents the common, non-variant form of the BRCA2 gene at this specific location. It is considered the reference sequence and is not associated with the pathogenic changes linked to hereditary breast and ovarian cancer syndrome for this variant.
This is the most common genotype found in the general population across all ancestries.
Pathogenic variant carrier
This genotype indicates you carry one copy of the rare BRCA2 variant (c.7879A>T), which is classified as likely pathogenic. Research indicates this variant is associated with hereditary breast and ovarian cancer syndrome and may affect the protein's ability to perform DNA repair. Please discuss these results with a genetic counselor or your healthcare provider to understand your personal risk profile and appropriate screening options.
This variant is extremely rare and is not typically present in large population databases.
Rare homozygous variant
This genotype indicates you carry two copies of the rare BRCA2 variant (c.7879A>T). Because this variant is associated with hereditary breast and ovarian cancer syndrome, carrying two copies may have significant implications for your health and DNA repair function. It is essential to consult with a medical geneticist or oncologist to discuss the clinical significance of this finding and potential management strategies.
This genotype is exceptionally rare and has not been documented in standard population frequency databases.
What is the rs397509279 Variant?
The rs397509279 variant is a specific single nucleotide change in the DNA sequence of the BRCA2 gene. In scientific literature, this variant is also identified by its protein-level change, p.Ile2627Phe, or by the older nomenclature c.8107A>T. It is located within the DNA-binding domain of the BRCA2 protein, a region critical for the gene's function in maintaining genomic stability. Because this variant involves a change in a highly conserved region of the protein, researchers have investigated its impact on cellular processes. Studies have indicated that this specific alteration can impair the protein's ability to perform homology-directed repair, a vital mechanism cells use to fix damaged DNA. Consequently, this variant is recognized in clinical databases as a pathogenic or likely pathogenic finding.
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 central role in repairing damaged DNA, specifically through a process called homologous recombination. By helping to fix double-strand breaks in DNA, the BRCA2 protein ensures that genetic information is accurately copied and maintained when cells divide. When a person inherits a harmful or pathogenic variant in one copy of the BRCA2 gene, their cells may be less efficient at repairing DNA damage. Over time, this accumulation of unrepaired genetic errors can increase the risk of developing certain types of cancer, most notably breast and ovarian cancer. It is important to note that inheriting a pathogenic variant does not guarantee that an individual will develop cancer, but it does significantly alter the statistical risk profile compared to the general population.
Research and Clinical Evidence
The evidence supporting the classification of rs397509279 as pathogenic is derived from multiple sources, including clinical testing reports and functional laboratory studies. This variant has been identified in families and individuals with a history of breast and ovarian cancer. Beyond clinical observations, researchers have utilized functional assays to test how this specific mutation affects the BRCA2 protein's activity. These experiments have demonstrated that the variant disrupts the protein's normal function, including its role in regulating centrosome amplification and supporting DNA repair. Because of this combination of clinical data and functional evidence, the variant is widely considered to have clinical significance. As with many rare variants, ongoing research continues to refine our understanding of the specific cancer risks associated with this mutation, and clinical management is typically guided by established guidelines for BRCA2 mutation carriers.
Population Frequency
The rs397509279 variant is considered extremely rare. It is generally absent from large-scale population databases such as gnomAD, which aggregate genetic data from hundreds of thousands of individuals across diverse ancestries. Because it is not found in the general population at any significant frequency, its presence in an individual is typically identified through targeted clinical genetic testing rather than population-wide screening. The rarity of this variant underscores that it is not a common polymorphism but rather a specific, high-impact mutation that is usually tracked within families or identified during diagnostic workups for hereditary cancer syndromes.
Managing Genetic Information
If you have received a report indicating the presence of the rs397509279 variant, it is essential to discuss these results with a qualified healthcare professional, such as a genetic counselor or an oncologist. This information is complex and carries significant implications for personal and family health management. A clinician can help interpret what this result means for your specific medical history and discuss appropriate screening or risk-reduction strategies. It is important to remember that genetic testing results are not a diagnosis of cancer, nor do they predict with certainty that cancer will occur. You should never make medical decisions based solely on a genetic report without professional guidance. A healthcare provider can provide the necessary context, explain the limitations of the data, and help you navigate the next steps in your healthcare journey.
How common is this variant?
The rs397509279 variant is extremely rare and is generally absent from large-scale population control databases.
Frequently asked questions
What does it mean to have a pathogenic BRCA2 variant?
A pathogenic variant in BRCA2 means there is a known, harmful change in the gene that impairs its ability to repair DNA. This increases the lifetime risk of developing certain cancers, such as breast and ovarian cancer.
Does having this variant mean I will definitely get cancer?
No. Having a pathogenic BRCA2 variant increases your risk of developing cancer compared to the general population, but it does not guarantee that you will develop the disease. Many factors, including lifestyle and other genetic influences, contribute to cancer risk.
Should I be worried if I have this variant?
It is natural to have concerns, but it is important to speak with a genetic counselor or doctor. They can provide personalized information, explain your specific risk levels, and discuss appropriate medical management or screening options.
How is this variant different from a VUS?
A pathogenic variant has strong evidence showing it disrupts gene function and increases disease risk. A Variant of Uncertain Significance (VUS) is a change where there is currently not enough evidence to determine if it is harmful or benign.
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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A pathogenic variant in BRCA2 identified in clinical screening cohorts as a significant contributor to hereditary cancer risk.
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.