Abstract
Locus Reference Genomic (LRG; http://www.lrg-sequence.org/) records contain internationally recognized stable reference sequences designed specifically for reporting clinically relevant sequence variants. Each LRG is contained within a single file consisting of a stable ‘fixed’ section and a regularly updated ‘updatable’ section. The fixed section contains stable genomic DNA sequence for a genomic region, essential transcripts and proteins for variant reporting and an exon numbering system. The updatable section contains mapping information, annotation of all transcripts and overlapping genes in the region and legacy exon and amino acid numbering systems. LRGs provide a stable framework that is vital for reporting variants, according to Human Genome Variation Society (HGVS) conventions, in genomic DNA, transcript or protein coordinates. To enable translation of information between LRG and genomic coordinates, LRGs include mapping to the human genome assembly. LRGs are compiled and maintained by the National Center for Biotechnology Information (NCBI) and European Bioinformatics Institute (EBI). LRG reference sequences are selected in collaboration with the diagnostic and research communities, locus-specific database curators and mutation consortia. Currently >700 LRGs have been created, of which >400 are publicly available. The aim is to create an LRG for every locus with clinical implications.
Highlights
Accurate and unambiguous annotation of disease-causing variants is essential
The lack of accepted and stable reference sequences for variant reporting resulted in the use of different sequences and inconsistency of variant reporting over time
Designed for the reporting of diagnostically relevant variants, an Locus Reference Genomic (LRG) provides a stable reference sequence record for a particular genomic locus: genomic DNA, transcript and protein sequences are all included in one record, thereby providing a concise ‘one-stop’ record for variant reporting in all coordinates
Summary
Accurate and unambiguous annotation of disease-causing variants is essential. Central to this is the reference DNA sequence with respect to which a variant is reported. Collaborators are asked to review the pending LRG record, provide information on any alternative reference sequences they currently use and are advised on how to switch to reporting variants using LRGs. During the creation process, additional transcripts can be added to the LRG record at the recommendation of a member of the community. The fixed section contains the core information for the LRG (Figure 2), including requester information, the LRG reference sequences, a unique identifier in the format ‘LRG_[number]’, the HUGO Gene Nomenclature Committee (HGNC) [3] gene identifier and LRG-specific exon numbering.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
