HEXA rs28937900: Understanding the c.1073+1G>A Variant
The rs28937900 variant, also known as c.1073+1G>A, is a genetic change in the HEXA gene that disrupts the normal processing of genetic instructions. It is recognized as a pathogenic variant associated with Tay-Sachs disease, a condition that affects the body's ability to break down certain fatty substances.
What each genotype means
Typical risk profile
You carry two reference copies at this splice site in the HEXA gene and do not carry the c.1073+1G>A pathogenic variant. This genotype does not indicate an increased risk of being a carrier for Tay-Sachs disease via this specific variant. However, it does not completely eliminate carrier risk for other rare variants across HEXA.
Carried by over 99% of individuals across most global populations.
Tay-Sachs carrier
You carry one copy of the c.1073+1G>A splice junction variant, classifying you as a carrier for autosomal recessive Tay-Sachs disease. Heterozygous carriers generally do not show symptoms of HEXA deficiency because one functional copy produces sufficient beta-hexosaminidase A activity. If planning a pregnancy, carrier screening for reproductive partners and genetic counseling can help clarify family planning options.
Found in approximately 1 in 30 individuals of Ashkenazi Jewish ancestry, but observed at much lower rates (around 1 in 250 to 1 in 300) in the general population.
Tay-Sachs disease risk
Carrying two copies of the c.1073+1G>A splice mutation disrupts normal splicing in HEXA, which causes severe deficiency of beta-hexosaminidase A enzyme activity. In medical genetics, biallelic pathogenic loss-of-function variants in HEXA are associated with clinical Tay-Sachs disease, typically presenting in infancy. Individuals or families with this result typically review clinical management and supportive care options with a metabolic geneticist.
Extremely rare globally, occurring in roughly 1 in 3,600 live births in higher-risk founder populations and fewer than 1 in 300,000 in the general population.
What is the rs28937900 Variant?
The rs28937900 variant is a specific change in the DNA sequence of the HEXA gene, located on chromosome 15. In scientific literature, it is frequently referred to as c.1073+1G>A or IVS9+1G>A. This variant occurs at a canonical splice donor site, which is a critical junction where the cell's machinery cuts and pastes genetic information to create a functional blueprint for a protein. By altering a highly conserved nucleotide at this junction, the variant interferes with the correct splicing of the HEXA gene's messenger RNA. This disruption typically leads to the production of a nonfunctional or unstable protein, preventing the cell from creating the necessary enzyme components required for normal metabolic processes.
The Role of the HEXA Gene
The HEXA gene provides the instructions for building the alpha subunit of an enzyme called beta-hexosaminidase A. This enzyme is essential for the function of lysosomes, which are the recycling centers of the cell. Specifically, beta-hexosaminidase A is responsible for breaking down a fatty substance known as GM2 ganglioside. When the HEXA gene contains a pathogenic variant like rs28937900, the resulting enzyme activity is severely reduced or absent. Without enough functional enzyme, GM2 ganglioside cannot be properly degraded and instead accumulates to toxic levels, particularly within the neurons of the central nervous system. This accumulation is the underlying cause of the neurological symptoms associated with Tay-Sachs disease.
Research and Clinical Significance
Research has firmly established the rs28937900 variant as pathogenic in the context of Tay-Sachs disease. It is identified as a cause of the acute infantile form of the condition, which is characterized by progressive neurological decline. Because Tay-Sachs disease is an autosomal recessive condition, an individual must typically inherit two copies of a pathogenic variant—one from each parent—to manifest the disease. Carriers, who possess only one copy of the variant, generally do not show symptoms of the disease. The evidence for this variant's impact is strong, and it is routinely included in carrier screening panels for individuals of Ashkenazi Jewish descent, as well as other populations where the variant has been identified.
What You Can Do With This Information
Genetic information regarding carrier status is primarily used for reproductive planning and family health awareness. If you have received results indicating you are a carrier of the rs28937900 variant, it does not mean you have or will develop Tay-Sachs disease. However, it does mean there is a possibility of passing the variant to your children. If both parents are carriers of a pathogenic HEXA variant, there is a 25% chance with each pregnancy that the child will inherit two copies and be affected by the condition. This information is best discussed with a certified genetic counselor or a medical professional who can provide context based on your specific family history and reproductive goals. Never use genetic data to make independent medical decisions; always consult with a clinician to understand the implications of your results.
How common is this variant?
The rs28937900 variant is rare in the general population but is a known founder mutation in the Ashkenazi Jewish community, where the carrier frequency for Tay-Sachs variants is approximately 1 in 27 to 1 in 30.
Frequently asked questions
What is the difference between being a carrier and having Tay-Sachs disease?
A carrier has one copy of a pathogenic variant and one normal copy, which is usually sufficient for the body to produce enough enzyme to remain healthy. A person with Tay-Sachs disease has two copies of a pathogenic variant, leading to a severe deficiency of the enzyme.
Is rs28937900 the only variant that causes Tay-Sachs?
No, there are over 200 known variants in the HEXA gene that can cause Tay-Sachs disease. The rs28937900 variant is just one of several common mutations identified in specific populations.
Should I get tested for this variant?
Carrier screening is often recommended for individuals of Ashkenazi Jewish, French-Canadian, or Cajun descent, or those with a family history of Tay-Sachs. You should discuss the benefits and limitations of genetic testing with your healthcare provider or a genetic counselor.
Can this variant be treated?
Currently, there is no cure for Tay-Sachs disease, and management focuses on supportive care to address symptoms. Genetic testing is primarily used for carrier identification and reproductive counseling rather than for treating the variant itself.
Sources & further reading
Educational information only, last refreshed 10/27/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Pathogenic splice-junction variant (c.1073+1G>A / IVS9+1G>A) causing Tay-Sachs disease when in compound heterozygosity or homozygosity.
Pathogenic splice donor variant (c.1421+1G>C) in HEXA underlying carrier status for autosomal recessive infantile Tay-Sachs disease.
This HEXA variant is associated with Tay-Sachs disease, particularly late-onset forms.
Pathogenic splice junction mutation (c.1421+1G>C) in HEXA leading to Tay-Sachs disease.
Pathogenic HEXA splice donor site mutation (c.1073+1G>A) causing Tay-Sachs disease, common in carrier screening panels for Ashkenazi Jewish and French Canadian ancestry.
A 4-bp insertion (c.1278dupTATC) in HEXA that accounts for over 70% of Tay-Sachs disease alleles in Ashkenazi Jewish carrier screening panels.