2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Validation of parent of origin detection for de novo events identified on SNP microarray in a postnatal population

Validation of parent of origin detection for de novo events identified on SNP microarray in a postnatal population

Pdf Summary

The study aimed to validate the use of NxClinical software for determining the parent of origin for de novo copy number variants (CNVs) and regions of absence of heterozygosity (AOH) identified on SNP microarrays. The software utilizes informative SNP probes and b-allele frequency values to determine the parent of origin. The study analyzed 37 trio cases and evaluated the accuracy of determining de novo vs inherited events. The results showed that for accurate determination, the trio quality check measurement must be below certain thresholds (<1% for duo and <5% for trio). If the trio quality check is above these thresholds, the sample is rejected. The study found that calls with insufficient data had a median probe count of 47 and a likelihood ratio of under 10, while calls with sufficient data had a median likelihood ratio of 1.21E+07. For de novo analysis, 68% of de novo events had sufficient data for a parent designation, and 34% of de novo events were CNVs with sufficient data. The study did not observe a paternal bias for parent of origin of de novo events. The study also highlighted the importance of better characterizing false positive, false negative, and true positive calls through orthogonal confirmation. The detection of parent of origin for CNVs or AOH is critical for variant classification and communicating clinical impact. The study provided guidance for laboratories considering including this information in trio SNP microarray analyses. Further research is recommended for improving the determination of parental origin.

Asset Subtitle

Presenting Author - Megan Martin, MS, CGC; Co-Author - Brittany Brassell, MS, CGC, CG(ASCP)CM; Co-Author - Daniel Saul, MS; Co-Author - Brian Lee, Ph.D.; Co-Author - Moises Serrano, PhD;

Meta Tag

Clinical Cytogenetics

Genetic Testing

Imprinting

Microarray

Co-Author Brittany Brassell, MS, CGC, CG(ASCP)CM

Co-Author Daniel Saul, MS

Co-Author Brian Lee, Ph.D.

Co-Author Moises Serrano, PhD

Presenting Author Megan Martin, MS, CGC

Keywords

NxClinical software

parent of origin determination

copy number variants

absence of heterozygosity

SNP microarrays

informative SNP probes

trio cases

de novo events

trio quality check measurement

sufficient data calls