Premium
Variants of uncertain significance in prenatal microarrays: a retrospective cohort study
Author(s) -
Mardy AH,
Wiita AP,
Wayman BV,
Drexler K,
Sparks TN,
Norton ME
Publication year - 2021
Publication title -
bjog: an international journal of obstetrics and gynaecology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.157
H-Index - 164
eISSN - 1471-0528
pISSN - 1470-0328
DOI - 10.1111/1471-0528.16427
Subject(s) - omim : online mendelian inheritance in man , mendelian inheritance , phenotype , microarray , genetics , clinical significance , penetrance , dna microarray , copy number variation , microarray analysis techniques , biology , gene , significance analysis of microarrays , medicine , bioinformatics , pathology , gene expression , genome
Objective To categorise the variants of uncertain significance found with prenatal chromosomal microarray and determine the proportion of such variants that are associated with a well‐known phenotype in order to establish how often they remain truly of uncertain significance. Design Retrospective cohort study. Setting The University of California, San Francisco. Population All patients with a variant of uncertain significance on prenatal microarray between 2014 and 2018. Methods Each variant was classified as a copy number variant that (a) contains Online Mendelian Inheritance in Man (OMIM)‐annotated disease‐causing genes (‘OMIM morbid genes’); (b) confers autosomal recessive carrier status; (c) is associated with incomplete penetrance; (d) is >1 Mb in size without OMIM morbid genes; (e) demonstrates mosaicism; or (f) contains significant regions of homozygosity. For each variant of uncertain significance, we examined the existing literature to determine whether the predicted phenotype(s) was known. Main outcome measure Prevalence and classification of variants and how much information is available regarding the likelihood of an affected phenotype. Results Of 970 prenatal microarrays, 55 (5.8%) had at least one variant of uncertain significance. The most common were copy number variants containing OMIM morbid genes (36.8%). In all, 48 (84.2%) were associated with a known phenotype; 55 (96.5%) had data available regarding the likelihood of an affected phenotype. Conclusions The prevalence of variants of uncertain significance with prenatal microarray was 5.8%. In the large majority of cases, data were available regarding the predicted phenotype. Tweetable abstract Variants of uncertain significance occur in 5.8% of prenatal microarrays. In the overwhelming majority of cases, outcome information is available.