DECIPHER: database for the interpretation of phenotype-linked plausibly pathogenic sequence and copy-number variation

Abstract

The DECIPHER database (https://decipher.sanger.ac.uk/) is an accessible online repository of genetic variation with associated phenotypes that facilitates the identification and interpretation of pathogenic genetic variation in patients with rare disorders. Contributing to DECIPHER is an international consortium of >200 academic clinical centres of genetic medicine and ≥1600 clinical geneticists and diagnostic laboratory scientists. Information integrated from a variety of bioinformatics resources, coupled with visualization tools, provides a comprehensive set of tools to identify other patients with similar genotype–phenotype characteristics and highlights potentially pathogenic genes. In a significant development, we have extended DECIPHER from a database of just copy-number variants to allow upload, annotation and analysis of sequence variants such as single nucleotide variants (SNVs) and InDels. Other notable developments in DECIPHER include a purpose-built, customizable and interactive genome browser to aid combined visualization and interpretation of sequence and copy-number variation against informative datasets of pathogenic and population variation. We have also introduced several new features to our deposition and analysis interface. This article provides an update to the DECIPHER database, an earlier instance of which has been described elsewhere [Swaminathan et al. (2012) DECIPHER: web-based, community resource for clinical interpretation of rare variants in developmental disorders. Hum. Mol. Genet., 21, R37–R44].

Effectiveness of whole-exome sequencing and costs of the traditional diagnostic trajectory in children with intellectual disability

“…sanger.ac.uk), with a strong similarity between our patient's phenotype and the reported phenotype. [23][24][25] Further functional work and similar patients with variants in CHD4 are required to establish causality. A clinical geneticist returned the WES results to the patients and parents.…”

Axons to Exons: the Molecular Diagnosis of Rare Neurological Diseases by Next-Generation Sequencing

“…For example, PhenomeCentral summarizes information about other phenotypically similar patients with deleterious-appearing variants in the same candidate gene and allows these researchers to contact each other when a match is made (http://phenomecentral.org). Other similar Bmatchmaking^databases have been developed, such as GeneMatcher [52], which connects investigators based on their interest in the same gene, and DECIPHER [53], which allows investigators to search coded phenotypic and genotypic data to identify possible matches. The University of Miami GEM.app i s a d a t a b a s e t h a t sh a r e s e x o m e r e s u l t s f r o m researchers internationally to identify clinically relevant variants in a number of neurological disorders (e.g., hereditary spastic paraplegia, Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis) to identify novel genes [54].…”

Connecting the CNTNAP2 Networks with Neurodevelopmental Disorders

“…It should be noted, however, that DECIPHER lists disruptions and heterozygous losses of CNTNAP2, which have been inherited from healthy parents ( fig. 2 , red-framed bars) [Bragin et al, 2014]. While the Database of Genomic Variants [MacDonald et al, 2013] lists a number of phenotypically neutral CNVs within CNTNAP2 , the burden of CNVs in CNTNAP2 is not elevated in individuals with ID and autism [Cooper et al, 2011;Sanders et al, 2011].…”