Details

Autor(en) / Beteiligte

• Jurgens, Julie
• Ling, Hua
• Hetrick, Kurt
• Pugh, Elizabeth
• Schiettecatte, Francois
• Doheny, Kimberly
• Hamosh, Ada
• Avramopoulos, Dimitri
• Valle, David
• Sobreira, Nara

Titel

Assessment of incidental findings in 232 whole-exome sequences from the Baylor-Hopkins Center for Mendelian Genomics

Ist Teil von

• Genetics in medicine, 2015-10, Vol.17 (10), p.782-788

Ort / Verlag

United States: Elsevier Limited

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• In March 2013 the American College of Medical Genetics and Genomics published a list of 56 genes with the recommendation that pathogenic and likely pathogenic variants detected incidentally by clinical sequencing be reported to patients. As an initial step in determining the practical consequences of this recommendation in the research setting, we searched for variants in these genes in 232 whole-exome sequences from the Baylor-Hopkins Center for Mendelian Genomics. We identified rare, nonsynonymous, and splicing single-nucleotide variants and insertions/deletions and assessed variant classification using the Human Gene Mutation, Emory, and ClinVar databases. We analyzed the burden of mutation in each of the 56 genes and determined which variants should be reported to patients. Our filtering resulted in 249 distinct variants, with a mean of 1.69 variants per individual. Half of these were novel missense mutations not classified by any of the three reference databases. Of 101 variants listed in the Human Gene Mutation Database, 48 were also in ClinVar and 3 were also in Emory; half of these shared variants were classified discordantly between databases. Some genes consistently had greater variation than others. In total, 0.86% of individuals had a reportable incidental variant. These observations demonstrate some current challenges of assessing phenotypic consequences of incidental variants for counseling patients.