Estimation of carrier frequencies utilizing the gnomAD database for ACMG recommended carrier screening and Finnish disease heritage conditions in non-Finnish European, Finnish, and Ashkenazi Jewish populations.
Am J Med Genet A
; 194(7): e63588, 2024 07.
Article
em En
| MEDLINE
| ID: mdl-38459613
ABSTRACT
American College of Medical Genetics and Genomics (ACMG) recommends offering Tier 3 carrier screening to pregnant patients and those planning a pregnancy for conditions with a carrier frequency of ≥1/200 (96 genes for autosomal recessive [AR] conditions). Certain AR conditions referred to as Finnish disease heritage (FINDIS) have a higher prevalence in Finland than elsewhere. Data from gnomAD v2.1 were extracted to assess carrier frequencies for ACMG-recommended AR and FINDIS AR and X-linked genes in Finnish, non-Finnish European, and Ashkenazi Jewish populations. Following variants were considered ClinVar pathogenic or likely pathogenic, loss-of-function, and Finnish founder variants. Gene carrier (GCR), cumulative carrier (CCR), and at-risk couple rates (ACR) were estimated. In Finnish population, 47 genes had a GCR of ≥0.5%. CCRs were 52.7% (Finnish), 48.9% (non-Finnish European), and 58.3% (Ashkenazi Jewish), whereas ACRs were 1.4%, 0.93%, and 2.3% respectively. Approximately 141 affected children with analyzed AR conditions are estimated to be born in Finland annually. Eighteen genes causing FINDIS conditions had a GCR of ≥0.5% in the Finnish population but were absent in the ACMG Tier 3 gene list. Two genes (RECQL4 and RMRP) had GCR of ≥0.5% either in non-Finnish Europeans or Ashkenazi Jewish populations. Results highlight the need for careful curation of carrier screening panels.
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Base de dados:
MEDLINE
Assunto principal:
Judeus
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Testes Genéticos
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Triagem de Portadores Genéticos
Limite:
Female
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Humans
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Male
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Pregnancy
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article