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2023 ACMG Annual Clinical Genetics Meeting Digital ...
A database of high allele frequency variants from ...
A database of high allele frequency variants from exome sequencing data of 20,455 patients enriched with Asian population
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The document discusses the classification of variants in genetic disorders based on their allele frequency. The authors analyzed a total of 153,614 variants from their internal variant database, with around 77,000 variants associated with autosomal dominant (AD) diseases, 65,000 with autosomal recessive (AR) diseases, and 12,000 with X-linked (XL) diseases. Manual curation was performed on 6,822 variants found in ClinVar, resulting in 222 variants for AD diseases, 14 variants for AR diseases, and 3 variants for XL diseases being classified as likely benign (LB) with high confidence. Variants that couldn't be classified as LB were those that were extremely rare internally or found in genes with incomplete penetrance or variable expressivity.<br /><br />The authors highlight the importance of allele frequency information in variant classification and diagnosis of rare genetic disorders. They show that seemingly private variants can be classified as likely benign if they are commonly found only in certain ethnic groups or populations. The authors stress the need for more exome and genome sequencing in underrepresented populations to improve variant interpretation.<br /><br />To estimate ethnicity scores for each sample, a variant frequency table was created using gnomAD data, with common variants meeting specific conditions. The authors then calculated the conditional probability of each variant group occurring from each ethnic group and normalized it by the geometric mean. Based on these scores, an ethnicity was assigned to each sample.<br /><br />In conclusion, the authors propose a method for classifying variants based on allele frequency and highlight the importance of considering ethnic diversity in variant interpretation. Manual curation of variants is necessary, but they expect that a similar percentage of internal variants not found in ClinVar could also be classified as LB with high confidence.
Asset Subtitle
Presenting Author - Kisang Kwon, MS; Co-Author - Seong-in Hyun, Ph.D; Co-Author - Heonjong Han, Ph.D; Co-Author - Go Hun Seo, MD, Ph.D.; Co-Author - Hane Lee, Ph.D;
Meta Tag
Bioinformatics
Databases
Exome sequencing
NextGen Sequencing
Population Genetics
Sequencing
Variant Detection
Co-Author
Seong-in Hyun, Ph.D
Co-Author
Heonjong Han, Ph.D
Co-Author
Go Hun Seo, MD, Ph.D.
Co-Author
Hane Lee, Ph.D
Presenting Author
Kisang Kwon, MS
Keywords
classification
variants
genetic disorders
allele frequency
autosomal dominant
autosomal recessive
X-linked
likely benign
ethnicity
variant interpretation
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