10 - Evaluating Genomic Variants Flashcards
(30 cards)
Purpose of genetic testing
- Accurate molecular diagnosis
- Disease prognosis
- Cascade screening (family members)
- Screening
- Monitoring
Pathogenic variant
Capable of causing disease
Benign variant
Not harmful in effect
Mutation
ONLY pathogenic/disease causing variants
Polymorphism
Variant that is common in a normal population
Targeted detection of diagnostic variant
- Focuses on a specific gene location, size or region, and/or type of variant
- Diseases associated
Why are these restrictions of detection chosen
- Ease of interpretation
- Proven clinical utility
- Limited resources
Are all variants in an individuals DNA disease causing
Nah
Steps in determining variant pathogenicity
- Determine if variant is known or novel (via disease associated or normal variant databases, literature)
- Seen locally?
- Critically appraise the evidence
Nonsense and frameshift mutation pathogenicity
Assumed disease causing, provided that a loss of function/dominant negative effect is supported
Synonymous variants and mutations not near genes pathogenicity
Assumed to be non disease causing
Missense mutation pathogenicity
may have no effect, loss of function or gain of function
Mutation
Change in DNA sequence that is probably disease causing
Variant
Change in DNA sequence
Mod of inheritance
Dominant, recessive, X linked, autosomal
Alleles/zygosity
Heterozygous, homozygous, compound heterozygous, hemizygous
Genomic location
Coding, promoter/regulatory, splice site
Molecular change
- Substitution (synonymous, missense, nonsense)
- Deletion/insertion
Functional effect
Loss/gain of function
Homozygous
Same mutation present on both alleles
Heterozygous
Mutation present on one allele only
Compound heterozygous
Two different mutations present, one on each allele
Hemizygous
On sex chromosomes, A mutation on one allele, and the other allele is absent
De novo variant
Mutation found in child but not parents and is usually dominant disease
