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
in 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Jews
/
Genetic Testing
/
White People
/
European People
/
Genetic Carrier Screening
Limits:
Female
/
Humans
/
Male
/
Pregnancy
Country/Region as subject:
Europa
Language:
En
Journal:
Am J Med Genet A
Journal subject:
GENETICA MEDICA
Year:
2024
Type:
Article
Affiliation country:
Finland