Reclassification of a frequent African-origin variant from PMS2 to the pseudogene PMS2CL.
Lynch syndrome
PMS2
PMS2CL
Sanger sequencing
next-generation sequencing
pseudogene
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
18
10
2019
revised:
09
12
2019
accepted:
26
12
2019
pubmed:
10
1
2020
medline:
23
7
2021
entrez:
10
1
2020
Statut:
ppublish
Résumé
Genomic analysis has become a mainstay in the investigation of cancer patients, especially for those suspected of harboring a heritable cancer predisposition syndrome. With ubiquitous short-read next-generation sequencing (NGS) technologies, these analyses can be complicated by the inappropriate alignment of variants to homologous genomic regions or pseudogenes. Using distinct primer sets specific to the gene and pseudogene, a nonspecific primer set, and a highly gene-specific long-range polymerase chain reaction primer set, we have shown that in at least a subset of patients, the common African PMS2 variant NM_000535.5:c.2182_2184delACTinsG, classified as pathogenic in ClinVar, has been incorrectly assigned to PMS2 from its well-documented pseudogene, PMS2CL. This result is not only important for patients but also highlights a weakness in short-read NGS technologies and the racial inequity in genomic analysis.
Substances chimiques
PMS2 protein, human
EC 3.6.1.-
Mismatch Repair Endonuclease PMS2
EC 3.6.1.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
749-752Subventions
Organisme : CIHR
ID : FDN‐148390
Pays : Canada
Informations de copyright
© 2020 Wiley Periodicals, Inc.
Références
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