BRCA2 rs11571834: Understanding the p.Lys3326Ter Variant
The genetic variant rs11571834 (also cataloged in close association with rs11571833) represents a nonsense mutation in the BRCA2 gene known as p.Lys3326Ter or K3326X. Unlike classic, high-penetrance BRCA2 mutations that cause classical Hereditary Breast and Ovarian Cancer syndrome, this variant introduces a stop codon near the very end of the protein that confers only a modest statistical increase in cancer susceptibility. Population studies have linked it to slightly elevated odds of developing breast, ovarian, and squamous cell lung cancers, though it functions primarily as a low-to-moderate risk modifier rather than a definitive disease-causing mutation.
What each genotype means
Typical risk profile
You carry two copies of the standard allele and do not have the BRCA2 p.Lys3326Ter premature stop variant. Research indicates this genotype is not associated with the modestly elevated risks of breast, ovarian, or lung cancers observed in variant carriers. Your baseline risks for these conditions remain aligned with general population averages and individual family background.
Found in approximately 98% to 99% of individuals of European ancestry and exceeds 99% in East Asian, African, and other non-European populations.
Modestly elevated cancer susceptibility
You carry one copy of the BRCA2 p.Lys3326Ter (also referred to as K3326X) nonsense variant. While standard clinical curation guidelines frequently classify this variant as benign or low penetrance for classic hereditary breast and ovarian cancer syndrome, large epidemiologic studies observe a modest increase in susceptibility to breast, ovarian, and lung (particularly squamous cell) cancers. This is a mild risk modifier rather than a high-risk pathogenic mutation, and individual disease outcomes depend heavily on personal lifestyle and broader genomic factors.
Carried in a heterozygous state by roughly 1% to 2% of people of European descent; it is substantially rarer in East Asian and African ancestries.
Increased cancer susceptibility
You carry two copies of the BRCA2 p.Lys3326Ter nonsense variant. Homozygous individuals have been reported in large genome-wide association cohorts with higher relative cancer susceptibility compared to non-carriers, although the variant retains substantial DNA repair capacity compared to classical severe BRCA2 mutations. Because this genotype is very rare and evidence on long-term clinical penetrance remains limited, findings should be interpreted with clinical genetics counseling rather than assumed to indicate definitive disease.
Extremely rare across all global ancestries, occurring in fewer than 1 in 10,000 individuals worldwide.
Genetic Nature and Location of rs11571834
The BRCA2 variant rs11571834 involves a single nucleotide alteration in the coding sequence of the BRCA2 gene, designated molecularly as c.9976A>T. This change converts an amino acid codon that normally codes for lysine at position 3326 into a premature termination signal (stop codon), denoted in the scientific literature as p.Lys3326Ter or K3326X. Because this premature stop codon is situated in exon 27 near the very carboxyl terminus (C-terminus) of the 3,418 amino acid BRCA2 protein, it results in the truncation of only the last 93 amino acids. Functional studies indicate that the resulting messenger RNA escapes nonsense-mediated decay and preserves key functional domains of the protein, including the critical BRC repeat motifs and the core DNA-binding regions necessary for typical genomic maintenance.
The Role of BRCA2 in DNA Repair
The BRCA2 gene codes for a vital tumor suppressor protein responsible for preserving genomic stability. Its primary cellular job is to coordinate homologous recombination, an essential, high-fidelity repair mechanism that mends double-strand breaks in DNA. When typical pathogenic variants disrupt the critical core structures of BRCA2, cells lose the ability to accurately repair chromosomal damage, resulting in widespread genomic instability and a steeply elevated lifetime risk of breast, ovarian, prostate, and pancreatic malignancies. Because the p.Lys3326Ter alteration only truncates a small distal segment of the protein whose full biochemical role remains under investigation, cells carrying this change retain significant baseline repair capacity, leading to far milder clinical manifestations than classical loss-of-function BRCA2 alleles.
Published Associations and Evidence Strength
Large-scale consortia, such as the Collaborative Oncological Gene-environment Study (iCOGS), have evaluated the cancer risks linked to p.Lys3326Ter across tens of thousands of participants. Weighted regression models demonstrate a modest association with invasive breast cancer (odds ratio ~1.28) and ovarian cancer (odds ratio ~1.26), with slightly higher odds seen in estrogen receptor-negative subtypes. Separate genome-wide association studies have also observed an association with squamous cell lung cancer (odds ratio ~2.47) and cutaneous squamous cell carcinoma, especially in smokers and individuals exposed to environmental mutagens. Despite these statistical correlations, the overall evidence strength for direct high-grade disease causation remains classified as limited; clinical databases like ClinVar frequently designate the allele as benign or a low-penetrance risk factor for classical Hereditary Breast and Ovarian Cancer syndrome.
Interpreting Results and Clinical Perspective
Detecting a risk-associated allele at rs11571834 can provide helpful personal context, but it does not constitute a clinical diagnosis of hereditary cancer or mean an individual will develop cancer. Clinical guidelines do not treat the p.Lys3326Ter variant as a high-risk pathogenic mutation that warrants invasive prophylactic surgeries, such as risk-reducing mastectomy or oophorectomy. Instead, comprehensive cancer risk assessment depends on a patient's broader family health history, personal lifestyle factors, environmental exposures like smoking, and potential co-inherited genetic modifiers. Individuals with questions about personal or familial cancer patterns should discuss their genetic testing reports with a certified genetic counselor or physician rather than taking unilateral medical action based solely on an isolated genetic data point.
How common is this variant?
The minor T allele occurs with an allele frequency of approximately 0.008 to 0.01 (about 1%) in individuals of European ancestry, occurs at lower frequencies (0.004–0.007) in South Asian and Ashkenazi Jewish populations, and is extremely rare or absent in East Asian cohorts.
Frequently asked questions
Does having the rs11571834 variant mean I have hereditary breast cancer?
No. The rs11571834 variant confers only a small statistical increase in cancer risk and is not considered a classic pathogenic mutation for Hereditary Breast and Ovarian Cancer syndrome. Most individuals who carry this allele never develop cancer.
Is the p.Lys3326Ter variant treated the same as standard BRCA2 mutations?
No, clinical genetics guidelines do not manage this variant like classical high-risk BRCA2 disruptions. Preventative interventions like prophylactic surgery are not recommended based on this variant alone, as it functions more as a low-to-moderate risk modifier.
Why is rs11571834 linked to lung cancer as well as breast cancer?
Research indicates that minor defects in DNA repair can heighten vulnerability to environmental carcinogens such as tobacco smoke. Consequently, observational studies have found carriers to have higher odds of developing squamous cell lung cancers.
What should I do if my raw genetic data shows this variant?
You should share the result with a certified genetic counselor or your doctor to evaluate it alongside your personal and family medical history. They can help determine if routine, age-appropriate cancer screenings are sufficient or if additional assessments are warranted.
Sources & further reading
Educational information only, last refreshed 9/10/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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