A paper titled “Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology” was published by Genetics in Medicine today.

The article is freely available at here.

These recommendations apply to the genetic tests used in clinical laboratories, including whole genome and whole exome sequencing. This report recommends the use of specific standard terminology—“pathogenic,” “likely pathogenic,” “uncertain significance,” “likely benign,” and “benign” to describe variants identified in genes that cause Mendelian disorders. What is different from the 2007 guideline is that, this 2015 guideline now describes a formal process for classifying variants into these five categories based on a variety of criteria. These include measures such as population frequency of alleles, computational predictions of variant deleteriousness, the location of the mutations within a gene, the known disease model, and the tolerance of a gene for deleterious variants. This increase in complexity means that variant interpreation in clinical setting will be more time-consuming, but on the other hand, the results may be more reproducible across laboratories and more interpretable by physicians.