ArticleGenetics in medicine : official journal of the American College of Medical Genetics2020
Preconception carrier screening yield: effect of variants of unknown significance in partners of carriers with clinically significant variants.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed.
- Expanded Carrier Screening: Current Evidence and Future Directions in the Era of Population Genomics.Genes · 2026Review
- Advancements in Prenatal Genetic Screening and Testing: Emerging Technologies and Evolving Applications.Diagnostics (Basel, Switzerland) · 2025Review
- Rare diseases load through the study of a regional population.PLoS genetics · 2025Article
- The Excess of Carriers in Rare Disorders Suggests a Nonpathogenic Effect for Most Variants of Uncertain Significance.Clinical genetics · 2025Article
- Assessment the carrier frequency of monogenic diseases in populations requiring assisted reproductive technology.BMC medical genomics · 2024Article
- Ordering genetic testing by neurologists: points to consider.Journal of neurology · 2023Review
- Genome-wide data from medieval German Jews show that the Ashkenazi founder event pre-dated the 14Cell · 2022Article
- Assessment of an automated approach for variant interpretation in screening for monogenic disorders: A single-center study.Molecular genetics & genomic medicine · 2022Review
- Assessing clinical utility of preconception expanded carrier screening regarding residual risk for neurodevelopmental disorders.NPJ genomic medicine · 2022Article
- A capillary electrophoresis-based multiplex PCR assay for expanded carrier screening in the eastern Han Chinese population.NPJ genomic medicine · 2022Article
- Fine-scale population structure and demographic history of British Pakistanis.Nature communications · 2021Article
- Article
- The ethics of preconception expanded carrier screening in patients seeking assisted reproduction.Human reproduction open · 2021Article
- Equitable Expanded Carrier Screening Needs Indigenous Clinical and Population Genomic Data.American journal of human genetics · 2020Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeExpanded preconception carrier screening (ECS) identifies at-risk couples (ARCs) for multiple diseases. ECS reports currently include only pathogenic/likely pathogenic variants (P/LPVs). Variants of unknown significance (VUS) are not reported, unlike genomic or chromosomal array test results in other post/prenatal settings. Couples who are P/LP and VUS carriers (P/LP*VUS) may be at risk, particularly in genes with high P/LP carrier rates. We examined the possible contribution of P/LP*cVUS (coding, nonsynonymous VUS) matings to ECS yield in an Ashkenazi Jewish cohort, a population with well-established preconception screening.
methodsWe analyzed 672 Ashkenazi Jewish genome sequences (225,456 virtual matings) for variants in three different gene sets and calculated the rates of P/LP*P/LP and P/LP*cVUS matings.
resultsAcross 180 genes, we identified 4671 variants: 144 (3.1%) P/LP and 1963 (42%) VUS. Across gene sets, the proportion of P/LP*P/LP and P/LP*cVUS ARCs was 2.7-3.8% and 6.8-7.5%, respectively.
conclusionDisregarding VUS in ECS may miss ARCs. Even if only 10% of couples currently classified as P/LP*cVUS are ultimately reclassified as P/LP*P/LP, ECS yield would increase by ≈20%. While current understanding of VUS precludes VUS reporting in ECS, these findings underscore the importance of VUS reclassification. This will crucially depend on enlarging population frequency databases, especially of affected individuals.
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