When classifying genetic variants as benign or pathogenic, most labs rely on allele frequencies from gnomAD, the largest public repository of genome/exome sequence data. GnomAD combines data from several biobanks, control datasets as well as case-control studies covering several diseases, meaning that not all individuals in gnomAD are ‘healthy’. The breakdown of high-level study phenotype and case/control status for some exome samples shows that ~17% of all exomes are ‘cases’, including individuals with cardiac conditions, Type 2 diabetes, psychiatric conditions or inflammatory bowel disease. When classifying variants for these conditions, allele frequency thresholds should account for the possibility that a variant observed in gnomAD could be from an affected individual. The good news is that in gnomAD V4, cohorts recruited for severe pediatric disease have been removed, making it a good proxy for a healthy control population when classifying variants for severe pediatric diseases. For these disorders, it is unlikely that an affected individual will be represented in gnomAD and allele frequency thresholds should be set according. https://lnkd.in/gEWChGur
About us
At Zifo we provide specialized bioinformatics support and variant interpretation services to the clinical genomics industry. Our approach is rooted in a deep understanding of genome analysis, striving to support laboratories and healthcare professionals with accurate and reliable curation of genomic data. Join our page to stay informed about our latest developments in genomics research and services.
- Website
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www.zifornd.com
External link for Zifo Clinical Genomics
- Industry
- IT Services and IT Consulting
- Company size
- 1,001-5,000 employees
- Headquarters
- Deerfield, Illinois
- Specialties
- Clinical Variant Interpretation, Clinical Genomics, Bioinformatics, and NGS
Updates
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To build or buy? That is a question that many labs face when it comes to finding a #bioinformatics solution to support the analysis of next-gen sequence (#NGS) data for clinical #genetictesting. #precisionmedicine #genomics
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Can't wait to try out this new genetic prevalence estimator tool, GeniE, for estimating carrier frequency and disease prevalence for recessive disorders! https://lnkd.in/e4pUEYj8 #gnomad #ngs #genetictesting
Genetic Prevalence Estimator
genie.broadinstitute.org
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Check out our recent article where we present a methodology for determining which genes in a panel may be suitable for copy number variant analysis. #ngs #genetictesting
Is analysis of CNVs in gene panels worth the effort?
Zifo Clinical Genomics on LinkedIn
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Great work by WHO! Small, but important step to bring more global equity in newborn screening! https://lnkd.in/gGXQ6BRX
Genetic Counselor | Public Health Genetics and Rare Disease Consultant | Founder and CEO, Connetics Consulting LLC
This is fanastic news and so encouraging for the expansion of Newborn Screening into LMICs! We will absolutely be celebrating this more during International Society for Neonatal Screening ‘s International Neonatal Screening Day happening on June 28! https://lnkd.in/gU5Z3ZWd *************** WHO exhorts promotion of Newborn Screening... Please check P-5 of this draft resolution... Dr. Anshu Banerjee, the Director for Maternal, Newborn and Child Health at WHO got a paragraph about newborn screening approved as part of the resolution for policy implementation globally during the 77th World Health Assembly in Geneva last week. (OP)1. INVITES Member States, in accordance with national context and priorities: (6) to consider implementing a universal newborn screening programme including comprehensive birth defect screening, including specific needs and considerations for diagnosis, management and long-term care of children with birth defects.
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Many customers ask us about the impact of using different data sources for clinical genetic variant interpretation. Check out our latest article that explore the impact of using the latest version of gnomAD. #ngs #genetictesting #precisionmedicine
Transitioning from gnomAD V2 to V4: Impact on genetic variant classification
Zifo Clinical Genomics on LinkedIn
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Fantastic resources from the NHS!
Wouldn't it be good if signposting to genomics education and training, testing forms, key contacts within Clinical Genetics Services and Genomic Laboratory Hubs and patient support links were all in one place? We think so, which is why we made our 'Little Book of NHS Genomic Testing'. Find it on our website and request copies for yourself and colleagues: https://lnkd.in/eQj97hvX
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Terrific additional resource for variant allele frequencies. Will be interesting to se if they integrate with gnomAD at some point.
I am delighted to share that the RGC Million Exomes publication titled “A deep catalogue of protein-coding variation in 983,578 individuals" is out in Nature and can be accessed at https://rdcu.be/dIweL This was a massive effort supported by several Regeneron Genetics Center (RGC) colleagues. We are grateful to all our collaborators and research participants who made this work possible. Kudos to Kathie Sun for leading the analyses and taking the paper to completion and Xiaodong (Sheldon) Bai for taking on the mammoth task of making this harmonized variant dataset. Heartfelt thanks to coauthors Suying Bao, Chuanyi Zhang, Siying Chen, Josh Backman, Adam Locke, Manav Kapoor, Will Salerno, Jeffrey Reid, Jonathan Marchini, Gonçalo Abecasis, John Overton, Mona N., Evan Maxwell, Boris Boutkov, George Mitra, Tyler Joseph and several other RGC team members and RGC- ME cohort partners. Key takeaways from RGC-ME 1. RGC-ME is the largest dataset of coding variation derived from 983,578 individuals representing a diverse array of ancestries and includes over 10.4 million missense and 1.1 million predicted loss-of-function (pLOF) variants 2. All samples have been sequenced at the RGC and the data processed with a single sequencing and informatics protocol 3. This dataset includes 191,000 unrelated individuals of non-EUR ancestry providing an improved representation of allelic diversity useful for understanding rare variants 4. We identify 3,988 loss-of-function intolerant genes and 1,482 genes with regions depleted of missense variants despite being tolerant to pLOF variants 5. RGC-ME data includes some cohorts with high rates of relatedness, contributing to a comprehensive collection of homozygous loss-of-function variation in 4,686 genes. 6. RGC-ME browser (https://lnkd.in/etVrqt9U) provides genomic locations, fine-scale ancestry assignments and population-specific allele frequencies, alleles and annotations for 34,512,842 variants. 7. We estimate that 3% of individuals have a clinically actionable genetic variant, and that 11,773 variants reported in ClinVar with unknown significance are likely to be deleterious cryptic splice sites. 8. We hope that RGC-ME data and browser will be a useful resource for understanding rare variants and genetics-informed precision medicine.
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Most clinical labs in the US rely on ClinGen's Dosage Sensitivity assessments when determining genetic mechanism of disease, especially for analysis of CNVs. What some labs might not know is that there is another similar resource available from EMBL-EBI called Gene2Phenotype (G2P). In this post, we explore the benefits of incorporating G2P's curated disease mechanisms for analysis of CNVs. ClinGen Resource European Bioinformatics Institute | EMBL-EBI #genecuration #genetictesting #ngs #precisionmedicine
Genetic mechanisms of disease: a comparison of ClinGen and Gene2Phenotype resources
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What a fantastic conference in NOLA this week! The Executive War College is a great conference to gain a macroeconomic view of the clinical laboratory industry. Excellent and timely discussions about FDA regulation of LDTs, etc. Thank you The Dark Intelligence Group for putting on a memorable event. #genetictesting
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