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Evaluation of Bayesian Point-Based System on the Variant Classification of Hereditary Cancer Predisposition Genes.
Eldomery, Mohammad K; Maciaszek, Jamie L; Cain, Taylor; Loyola, Victor Pastor; Mothi, Suraj Sarvode; Wheeler, David A; Tang, Li; Wang, Lu; Klco, Jeffery M; Blackburn, Patrick R.
Afiliación
  • Eldomery MK; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. Electronic address: mohammad.eldomery@stjude.org.
  • Maciaszek JL; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
  • Cain T; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
  • Loyola VP; Department of Computational Biology St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Mothi SS; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Wheeler DA; Department of Computational Biology St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Tang L; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
  • Wang L; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
  • Klco JM; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
  • Blackburn PR; Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Genet Med ; : 101276, 2024 Sep 18.
Article en En | MEDLINE | ID: mdl-39306722
ABSTRACT

PURPOSE:

To assess the differences in variant classifications using the ACMG/AMP 2015 guidelines and the Bayesian point-based classification system (here referred to as the point system) in 115 hereditary cancer predisposition genes and explore variant sub-tiering by the point system.

METHODS:

Germline variant classifications for 721 pediatric patients from an in-house panel were retrospectively evaluated using the two scoring systems.

RESULTS:

2376 unique variants were identified, with ∼23.5% exhibiting discordant classifications. Unique variants classified by the point system demonstrated a lower rate of variants of uncertain significance (VUS; ∼15%) compared to ACMG/AMP 2015 (∼36%). This change is attributed to unique variants with one benign supporting evidence (∼12%) or one benign strong evidence (∼4%) being classified as likely benign by the point system. Additionally, variants with conflicting/modified evidence (∼5% of 2376) are also resolved by the point system. Sub-tiering unique variants classified by the point system as VUS (n=354) indicates ∼77.4% were VUS-Low (0-1 points), while the remaining ∼22.6% were VUS-Mid (2-3 points) and VUS-High (4-5 points).

CONCLUSION:

The point system reduces the VUS rate and facilitates their sub-tiering. Future large-scale studies are warranted to explore the impact of the point system on improving VUS reporting and/or VUS clinical management.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Genet Med Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Genet Med Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos