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How common are variants of unknown significance?
In addition to its undeniable clinical utility, NGS is also unveiling a large number of variants that we are still not able to clearly define and classify, the variants of uncertain significance (VUS), which account for about 40% of total variants. At present, VUS use in the clinical context is challenging.
What is uncertain significance in genetic testing?
• Variant of uncertain significance (VUS): This means that the test found a genetic change, but there is not enough known about the change to give a diagnosis. In some cases, testing other family members can help us better understand what the genetic change means.
How do you read a gene variant?
Variants are usually detected by reading the DNA code, a method called DNA sequencing. A proper report always contains the variant described on the DNA level. In addition, a report usually contains a description of the predicted consequence of the variant on the protein, rarely the consequence on RNA.
How common are VUS?
Thousands are known; about 15% of test-takers get a VUS result. A breast cancer cell (NHGRI). The three common “Ashkenazi” mutations obliterate the BRCA1 and BRCA2 proteins because they disrupt the way that the DNA sequence is read in triplets.
What does unknown clinical significance mean?
In a small number of cases, genetic testing finds a “variant of unknown significance,” or VUS. This means there is a portion of the gene that looks different from the way it’s normally expected to look. However, researchers haven’t yet confirmed whether this variant is a harmless change or a risk factor for cancer.
What is unknown clinical significance?
A variant of uncertain (or unknown) significance (VUS) is a genetic variant that has been identified through genetic testing but whose significance to the function or health of an organism is not known.
What does abnormality of uncertain significance mean?
What does a variant in a gene mean?
(VAYR-ee-unt) An alteration in the most common DNA nucleotide sequence. The term variant can be used to describe an alteration that may be benign, pathogenic, or of unknown significance. The term variant is increasingly being used in place of the term mutation.
What does having a gene variant mean?
A gene variant is a permanent change in the DNA sequence that makes up a gene. This type of genetic change used to be known as a gene mutation, but because changes in DNA do not always cause disease, it is thought that gene variant is a more accurate term.
Should I worry about a VUS?
So how should a person react to a VUS? Genetic counselors say it should be considered along with the person’s other medical information, but not used as the sole reason for a major decision like breast removal. That message has not gotten through to some doctors, said Dr. Allison Kurian of Stanford University.
What disease is BRCA2 involved in?
The genes most commonly affected in hereditary breast and ovarian cancer are the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes. About 3% of breast cancers (about 7,500 women per year) and 10% of ovarian cancers (about 2,000 women per year) result from inherited mutations in the BRCA1 and BRCA2 genes.
How do you classify variants?
Variants are assigned a formal classification based on: Weighted evidence: The evidence gathered during variant review is scored based on the relative importance of the evidence type. Certain types of evidence may support a pathogenic classification while others may support a benign classification.
How to explain a variant of uncertain significance?
When communicating a VUS the first words out of your mouth should be planned to set the family at ease. Let them know first that the testing did not identify a genetic diagnosis for their child, and then tell them about the VUS. Remind them that variants are common and that they may be familial and/or benign, like freckles or red hair.
Can a genetic test re-classify a VUS?
Ideally, when genetic testing identifies a VUS, parental samples are available for testing and provide information that enables the lab to re-classify the variant. In practice this is often not the case.
What does it mean when genetic test results are inconclusive?
Showing a “variant of unknown significance” (i.e. inconclusive): Sometimes a genetic test finds an unusual change, or “variant,” in the genes, but not one that has been clearly associated with increased cancer risk. As more family members are tested, it may become clearer as to whether or not the variant is associated with cancer risk.
How is parental testing used to determine VUS?
Parental testing may clarify the classification of a VUS by determining whether the variant was inherited or arose de novo. I recognize that busy clinicians may not have as much time to delve into explaining genetics as some families need.