Clinical Variant Analysis for Cancer – Applying AMP Guidelines to Analyze Somatic Variants Somatic variants can manifest in different ways: Single Nucleotide Variants Indels Fusions and Copy Number Variations There is a difference between the interpretation of germline and somatic variants. The former is exclusively focused on establishing the level of pathogenicity vis a vis a particular disease. In contrast… Read more »
Clinical Variant Analysis for Cancer – Applying AMP Guidelines to Analyze Somatic Variants As described in my eBook “Genetic Testing for Cancer,” any bioinformatic pipeline for cancer ultimately calls variants based on the aligned reads that the sequencer generated. Variant calling is the process of reviewing a sequence alignment, typically in the form of a BAM file, to identify loci… Read more »
Clinical Variant Analysis for Cancer – Applying AMP Guidelines to Analyze Somatic Variants Analogous to the ACMG guidelines for germline mutations, the Association for Molecular Pathologists (AMP) has issued guidelines to assess and report on somatic variants. The key paper in this area was published by Li et. al (2017) with the title “Standards and Guidelines for the Interpretation and… Read more »
Clinical Variant Analysis for Cancer – Applying AMP Guidelines to Analyze Somatic Variants Precision Medicine uses genetic information from individual patients. This may include the following areas: Diagnosis Treatment Prevention Specifically, in the cancer space, data derived from Next-Gen Sequencing (NGS) is used to diagnose and prognose diseases, select a targeted therapy and potentially evaluate the suitability of a patient… Read more »
Overview VSClinical enables users to evaluate variants according to the ACMG guidelines in a high-throughput fashion and obtain consistent results and accurate variant interpretations. This feature is tightly integrated into our VarSeq platform as well, and when paired together, users can evaluate NGS data and obtain clinical reports all in one suite. Coupled with the ability to find novel or… Read more »
VSClinical provides a rapid-fire way to investigate any variant’s impact by following the ACMG Guidelines process for classification. We will be demonstrating this by looking at interesting examples of rare disorders and showcasing some evaluation steps users may deploy in their analysis. Our first example in this blog series is for a patient who has an indifference to pain, while… Read more »
Examples of Clinical Variant Interpretation with VSClinical In this chapter, I’d like to go through a few examples for variants that have been classified with the help of VSClinical. This will give you a better understanding of how data sources are actually being represented in the software and how those are used to make decisions on applicable criteria. It goes… Read more »
Rules for Combining Various Classification Criteria Now that we have a solid understanding of how the various criteria are meant to be applied, it’s time to look at how the evidence collectively leads to the clinical categorization of a variant. Let’s go through the rule framework for combining the various criteria. Pathogenic In order for a variant to be classified… Read more »
Clinical Variant Analysis – Classification Criteria of Benign Variants The classification of benign variants is overall simpler and more straightforward, with the majority of benign variants being eliminated through allele frequency in various population catalogs. BA1 If a variant is common in one or more population catalog, as indicated by the allele frequency associated by the appropriate sub-population, it can… Read more »
Clinical Variant Analysis – Classification Criteria of Pathogenic Variants The ACMG Guidelines are utilized for the interpretation of variants. They are primarily applied to diagnose suspected inherited (primarily Mendelian) disorders in a clinical diagnostic laboratory setting. While evaluating variants no matter what the origin, it is important to distinguish between variants that are pathogenic (i.e., causative) for a disease and a… Read more »
Clinical Variant Analysis – Applying ACMG Guidelines to Analyze Germline Diseases The clinical interpretation of genetic variants is time-consuming and requires strict attention to detail. Clinicians must thoroughly review any variants that could potentially cause disease using a complex set of guidelines. There are guidelines for the interpretation of variants relating to hereditary risk, germline diagnostics issued by the American… Read more »
I am excited to announce the release of my new eBook “Clinical Variant Analysis – Applying ACMG Guidelines to Analyze Germline Diseases“! You can download your complimentary by clicking on the button below. The clinical interpretation of variants in Next-Gen Sequencing is a quickly evolving field. While the body of knowledge is growing exponentially, experts have to derive sound, clinical decisions leveraging an… Read more »
In part one of this series, we discussed how the ACMG Classifier can be implemented in your filter chain to support a best practice workflow. To continue our discussion on best practices of VSClinical, this blog will shed light on other attributes of VSClinical that can add support to your evaluation. Specifically, we will explore how VSClinical can help users… Read more »
Even though GRCh37 is currently the most widely used human genome assembly, GRCh38 provides a more complete human reference genome, offers more accurate genomic analysis, and includes centromere and mitochondrial information. However, we’re getting ahead of ourselves. Perhaps start with how we got here. The Human Genome Project started this all off with the world’s largest biological collaboration project in… Read more »
