Leveraging cancer mutation data to inform the pathogenicity classification of germline missense variants.

Innovative and easy-to-implement strategies are needed to improve the pathogenicity assessment of rare germline missense variants. Somatic cancer driver mutations identified through large-scale tumor sequencing studies often impact genes that are also associated with rare Mendelian disorders. The use of cancer mutation data to aid in the interpretation of germline missense variants, regardless of whether the gene is associated with a hereditary cancer predisposition syndrome or a non-cancer-related developmental disorder, has not been systematically assessed.

VEPerform: a web resource for evaluating the performance of variant effect predictors.

Computational variant effect predictors (VEPs) are providing increasingly strong evidence to classify the pathogenicity of missense variants. Precision vs. recall analysis is useful in evaluating VEP performance, especially when adjusted for imbalanced test sets.

A missense variant effect map for the human tumor-suppressor protein CHK2.

The tumor suppressor CHEK2 encodes the serine/threonine protein kinase CHK2 which, upon DNA damage, is important for pausing the cell cycle, initiating DNA repair, and inducing apoptosis. CHK2 phosphorylation of the tumor suppressor BRCA1 is also important for mitotic spindle assembly and chromosomal stability. Consistent with its cell-cycle checkpoint role, both germline and somatic variants in CHEK2 have been linked to breast and other cancers.

Improving the Ethics Review of Qualitative Health Research: A Comparison of Review Practices and Suggestions for Improvement by Researchers and Members of Research Ethics Committees.

Most qualitative health research is subject to ethics review and approval by a research ethics committee (REC). While many studies have identified the challenges that current ethics review practices pose to qualitative health research, there is currently a call to move the research focus from the shortcomings of ethics review practices to the possibilities for improvement. The aim of this grounded theory study was to identify possibilities for improvement of current ethics review practices which can count on endorsement from qualitative health researchers and members of REC alike.