Practice Exam-Clinical Genomics

Clinical Genomics

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The document contains two practice exam questions related to clinical genomics, authored by Claudia Barnett.<br /><br />**Question 25225** asks when it is appropriate to apply the PVS1 (very strong) criterion for a nonsense variant in a gene implicated in an autosomal dominant disorder. To apply PVS1 at full strength, the loss of function must be an established mechanism of the disease. This is typically demonstrated by the presence of other protein loss-of-function (pLOF) variants, and the exon should not be alternatively spliced, or the nonsense variant should not occur in the last exon to ensure it undergoes nonsense-mediated decay. Option D is the correct choice: "If the variant occurs in an exon where multiple other pathogenic pLOF variants have occurred."<br /><br />**Question 25224** examines which type of genetic variation is more easily detected with exome sequencing compared to genome sequencing. Due to its higher coverage, exome sequencing is better at detecting mosaic variants with low allele fractions. Hence, the correct answer is Option C: "Mosaic variants."<br /><br />For the first question, the appropriate circumstances for applying PVS1 include understanding the mechanism of the disease linked to the variant and ensuring that alternative splicing or exon location does not negate the potential pathogenic impact. For the second question, the focus is on the advantages of exome sequencing over genome sequencing in detecting specific types of genetic variations, underscoring exome sequencing's ability to detect mosaicism effectively.

Keywords

clinical genomics

PVS1 criterion

nonsense variant

autosomal dominant disorder

protein loss-of-function

nonsense-mediated decay

exome sequencing

genome sequencing

mosaic variants

Claudia Barnett