BRCA2 rs11571833 and rs144848: DNA Repair and Cancer Research
Your cells regularly encounter DNA damage. Some damage affects individual DNA letters; other damage breaks both strands of the DNA molecule. BRCA2 helps cells repair these breaks, protecting the stability of their genetic information [R].
Two variants available for free in GeneExplorer offer different perspectives on this important gene:
You can explore both results in the free BRCA2 GeneExplorer report.
What Does the BRCA2 Gene Do?
BRCA2 produces a tumor suppressor protein that helps prevent uncontrolled cell growth by supporting DNA repair.
It participates in homologous recombination, a repair process that uses a matching DNA sequence as a template to repair breaks accurately. BRCA2 works with other repair proteins, including RAD51, to help carry out this process [R].
When certain pathogenic variants substantially disrupt BRCA2 function, damaged DNA can accumulate, increasing susceptibility to cancer. However, different changes in this large gene can have very different consequences [R].
For a related repair pathway, explore BRCA1 in GeneExplorer.
BRCA2 rs11571833: What Is K3326X?
Rs11571833 changes a DNA instruction from A to T. It is also written as c.9976A>T.
At protein position 3326, the T allele replaces an instruction for lysine with a stop signal. This is why the variant is called:
K3326X
Lys3326Ter
p.Lys3326
The resulting protein lacks its final 93 amino acids [R].
A premature stop can sound alarming, but its location and supporting evidence matter. K3326X occurs near the protein’s end, and expert review classifies it as benign for hereditary BRCA2-associated breast and ovarian cancer predisposition [R].
At the same time, large population studies have reported smaller cancer-risk associations. These findings describe a different scale of susceptibility from high-risk pathogenic BRCA2 variants.
Rs11571833: What Do AA, AT, and TT Mean?
Genotype | Interpretation |
AA | No copies of K3326X at this position. |
AT | One K3326X copy. Published studies have associated this variant with modestly increased odds of certain cancers. |
TT | Two K3326X copies. This genotype is rare, and a reliable genotype-specific cancer-risk estimate is unavailable. |
K3326X and Breast and Ovarian Cancer
A large international study analyzed data from 76,637 cancer cases and 83,796 controls across breast, ovarian, and prostate cancer investigations.
Researchers used statistical weighting to account for the possibility that K3326X carriers also carried another pathogenic BRCA2 variant.
Compared with noncarriers, K3326X carriers had:
Outcome | Reported association |
Breast cancer | Approximately 28% higher odds |
Invasive ovarian cancer | Approximately 26% higher odds |
The study did not find an association with prostate cancer [R].
What About Bladder and Other Urinary Tract Cancers?
A separate 2016 study examined K3326X using data from three genome-wide association studies.
Its meta-analysis reported approximately:
45% higher odds of urinary tract cancers overall.
60% higher odds of bladder cancer [R].
The researchers also performed a joint analysis that produced slightly different estimates. This explains why summaries may quote either a 45% or 47% increase for the combined cancer group.
How Can K3326X Be Benign Yet Have Risk Associations?
Clinical classification and population association studies answer related but different questions.
The benign classification indicates that K3326X is not considered a disease-causing variant responsible for the high-risk hereditary BRCA2 cancer syndrome [R].
Population studies ask whether it occurs more frequently among people with particular cancers. A variant can have a modest statistical association without behaving like a high-penetrance pathogenic variant. The mechanism also remains less settled than “shorter protein means failed DNA repair.” Published functional work has not consistently demonstrated impaired homologous recombination or sensitivity to DNA-damaging agents for K3326X [R].
The protein change is established; the full explanation for its reported cancer associations remains under investigation.
BRCA2 rs144848: What Is N372H?
Rs144848 is a different type of change. Also called c.1114A>C or N372H, it replaces asparagine (N) with histidine (H) at protein position 372. It does not introduce an early stop signal.
Genotype | Protein interpretation |
AA | Asn/Asn: both copies encode asparagine at position 372. |
AC | Asn/His: one copy encodes asparagine and one encodes histidine. |
CC | His/His: both copies encode histidine at position 372. |
N372H is classified as benign by an expert panel in ClinVar [R].
Researchers have investigated possible small cancer associations, but results have varied. A 2017 meta-analysis covering 40 studies found no statistically significant breast-cancer association in its overall allele comparison, although some subgroup analyses suggested small effects [R].
The evidence does not justify presenting CC as a high-risk BRCA2 result or claiming it establishes impaired DNA repair.
What Your BRCA2 Results Mean for You
These two markers illustrate why interpreting a gene requires looking at the specific variant. K3326X shortens the protein and has published population-level risk associations. N372H changes one amino acid and is classified as benign.
A significant personal or family history of breast, ovarian, pancreatic, or prostate cancer remains relevant regardless of these results. A clinician or genetic counselor can assess whether comprehensive clinical testing is appropriate [R].
Explore Your BRCA2 Results in GeneExplorer
BRCA2 connects everyday DNA maintenance with one of the most extensively studied areas of cancer genetics. K3326X and N372H provide two distinct examples of how genetic changes can differ in structure, research findings, and clinical significance.
Visit the free BRCA2 GeneExplorer report to explore both markers. You can analyze your existing raw DNA file in your browser to check which results are available.
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