PALB2 rs515726123: What Your Genotype Means
The rs515726123 variant is a pathogenic deletion in the PALB2 gene, known to increase susceptibility to hereditary breast, ovarian, and pancreatic cancers. Inheriting two copies of such pathogenic variants is associated with Fanconi anemia.
What each genotype means
Common normal genotype
This genotype represents the common or reference sequence for this location in the PALB2 gene. It is not associated with the increased cancer risks or Fanconi anemia conditions linked to pathogenic variants in this gene.
This is the most common genotype observed in the general population.
Increased cancer risk
This genotype involves a deletion (represented as -) and is associated with a 2-4 fold higher risk for breast cancer, depending on individual family history. You should discuss these findings with a genetic counselor or healthcare provider to understand your personal risk profile.
This is a rare genotype found in a small fraction of the population.
What is the rs515726123 Variant?
The rs515726123 variant is a specific type of mutation known as a frameshift deletion, where two nucleotides (GA) are deleted from the DNA sequence within exon 4 of the PALB2 gene. This deletion alters the reading frame of the genetic code, leading to a premature stop signal during protein production. Consequently, a shortened and non-functional PALB2 protein is created. The PALB2 protein is essential for normal cellular function, and this structural change prevents the gene from performing its vital biological role.
The Role of the PALB2 Gene
PALB2, which stands for Partner and Localizer of BRCA2, functions as a critical scaffolding protein that helps organize DNA repair machinery within cells. It collaborates with proteins produced by the BRCA1 and BRCA2 genes to repair double-strand breaks in DNA through a process called homologous recombination. This repair mechanism is vital for maintaining genomic stability. When PALB2 functions correctly, it prevents the accumulation of errors in the genetic code. Alterations in PALB2 can impair the cell's ability to fix DNA damage, potentially leading to the accumulation of harmful mutations and increasing the risk of cancer development.
Research and Clinical Evidence
Scientific research has established a strong association between pathogenic PALB2 variants, including rs515726123, and an elevated risk for several types of cancer. Clinical databases such as ClinVar classify this variant as pathogenic, indicating a broad scientific consensus that it is disease-causing. Studies have identified this specific variant in families with a history of breast, ovarian, and pancreatic cancers. While the evidence for its role in cancer predisposition is robust, it's important to recognize that cancer development is complex and influenced by a combination of genetic factors, environmental exposures, and lifestyle choices. An individual with this variant may have a higher risk, but it does not guarantee a cancer diagnosis.
Population Frequency
The rs515726123 variant is considered rare in the general global population, though its frequency can vary by ancestry and geographic region. Some research suggests this specific deletion may be a founder mutation in certain populations of Central European origin, potentially making it more common within those specific ancestral groups compared to the general population. Due to its rarity, most individuals do not carry this variant. Large-scale population databases, such as gnomAD, provide data on such variants, aiding scientists and clinicians in understanding their prevalence across diverse human groups.
Understanding Your Results
Interpreting information about this variant requires considering your personal health history. Carrying this variant indicates a genetic predisposition that might warrant proactive health management, but it does not mean you are currently ill or will definitely develop cancer. It is crucial to discuss your results with a healthcare provider or a genetic counselor. They can help you understand the implications for your specific risk profile and discuss appropriate screening or surveillance options. Never use this information to self-diagnose or make independent medical decisions regarding treatments, surgeries, or screenings, as professional guidance is essential for determining the best health management plan.
How common is this variant?
The rs515726123 variant is considered rare in the general global population, though its frequency can vary by ancestry and geographic region.
Frequently asked questions
Does having the rs515726123 variant mean I will get cancer?
No, having this variant increases your risk but does not guarantee a cancer diagnosis. Many factors, including other genes, lifestyle, and environmental influences, contribute to an individual's actual health outcome.
Can this variant skip a generation?
Genes themselves do not skip generations, but the observable impact of a variant can appear to. A parent can carry the variant without developing cancer and pass it to a child who may then develop a related condition, making it seem as if it skipped the parent.
What is the connection between PALB2 and Fanconi anemia?
PALB2 is also known as the FANCN gene. While carrying one copy is linked to cancer risk, inheriting two copies (one from each parent) is a known cause of Fanconi anemia, a rare genetic disorder characterized by bone marrow failure and other symptoms.
Should I get tested for other cancer genes?
If you carry this variant, a genetic counselor can provide expert advice on whether testing for other genes, such as BRCA1 or BRCA2, is appropriate based on your personal and family medical history.
Sources & further reading
Educational information only, last refreshed 10/4/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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