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Interpreting Your VUS Results

amazingposting by amazingposting
October 2, 2022
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VUS

A VUS is a genetic test that identifies mutations in a gene. Although the results of VUS can be confusing, genetic counselors can help you understand your VUS result. For example, one person in your family may test positive for an unknown variant that is believed to be responsible for increased cancer risk. Another person may test positive for a known cancer-related mutation that is less concerning than the unknown variant.

Variants of unknown/uncertain significance

Variants of unknown/uncertain significance (VUS) are genes that are associated with disease, but whose significance is unknown. This situation poses a dilemma for genetic counselling and screening methods. Whole-exome sequencing and other methods of genetic variation detection can detect VUS. New computational methodologies, such as the VariantClassifier, have been developed to shed light on this grey area. These methods combine polygenic risk prediction models and geneassociation networks.

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GEMINI11, a genome-wide association database, provides an in-silico framework to analyze and classify variants. It compares each variant with multiple genomic annotation sources. Other data sources include population genetics databases. ClinVar21 contains information on the pathogenicity of variants. In addition, scoring schemes are available to measure the impact of variants.

Variants of uncertain significance in cancer predisposition genes

Variants of uncertain significance (VUS) in cancer predisposition genes are those that are not yet classified as pathogenic or benign. They may be classified as benign when research indicates that they don’t affect the function of a gene. However, they can also be classified as pathogenic when more evidence is needed to determine their significance.

In the current study, 1,412 variants of uncertain significance were identified. Of these, 6.7% were reclassified within 6 years. The majority were categorized as benign or likely benign, while 5.9% were categorized as pathogenic. In addition, thirty-one percent of the patients with VUS had their management changed, which was reflected in the median time of one year between their discovery and their reclassification.

VarClass

Using a network-based approach to disease prediction, the VarClass in VUS method allows users to select variants associated with specific disease risk factors. It then combines those variants with baseline risk factors to compute risk prediction accuracy. The approach is tested on four different datasets: two datasets of individuals with intellectual disability, one dataset of individuals with gastric cancer, and a fourth dataset of individuals with Parkinson’s disease (PD). The datasets were analyzed using standard odds ratio analysis, which identified a set of variants associated with disease risk. The risk prediction accuracy was calculated for each dataset and compared to controls.

Variants found in VUS pose a dilemma for genetic counseling and screening methods. Researchers, health organizations, and research laboratories use whole exome sequencing to detect VUS. A novel computational methodology called the VariantClassifier uses gene-association networks and polygenic risk prediction models to illuminate the grey area of genetic variation in association with disease risk. The software has undergone several validation steps, and has been shown to accurately assign significance to disease risk genes and patients.

Interpretation of VUS results

Interpretation of VUS results can be challenging for both clinicians and patients. It is vital for a healthcare provider to understand the significance of the results and to discuss them with the patient. Genetic counseling is helpful in determining the best course of action, taking into account the patient’s family history and other risk factors. A genetic counselor should also be aware of any new developments or regulations regarding the use of VUS, since testing providers may differ in their policies on communicating results.

Some VUS results may be misinterpreted, and further studies may uncover variants that are not pathogenic. This leads to ethical and policy questions. Fortunately, several international efforts have been launched to standardize and refine the methods of interpreting VUS results. However, it is still important to remember that there are no universal standards for pathogenicity, and collaboration among researchers is vital.

Preimplantation genetic diagnosis

Preimplantation genetic diagnosis is a test that identifies a genetic abnormality in the offspring before birth. It can also confirm the diagnosis made by the parent and can pinpoint the exact genetic change that caused the condition. These tests usually involve chromosomal analysis, karyotyping, and multiple cells from the embryo. The cells are obtained from the chorionic villus or genetic amniocentesis.

Although preimplantation genetic diagnosis of VUS is not covered by insurance companies, it is an excellent way to prevent passing an abnormal gene mutation on to your child. The procedure requires time, effort, and expense, but it can give you peace of mind and help you make informed decisions about in-vitro fertilization.

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