To test your skills and knowledge in the context of Mendelian Genetics, please complete the 3 tasks below within the requested deadline.
Current exome/sequencing variant calls are standardly output in variant call format (VCF) format. We provided you with a small VCF file (Test_annotate.vcf - note this is in HG19) and ask you to check out the features of this file and process it further.
Task 1a: Use the provided Test_annotate.vcf to select only the SNPs using the Genomic Analysis Toolkit aka GATK (thus removing the INDELS). Provide us with the code you used to do this.
Task 1b: Annotate the SNP VCF file you just created using the Refseq and cytoBand databases with the latest standalone version of ANNOVAR. Use a 12bp splice boundary as an argument instead of the default splice boundary definitions.
- How many unique variants are in this file?
- How many “splicing” variants do you see in the refseq annotation?
- How many “startloss” variants do you see?
Task 1c: Write a short methods section (similar as for a peer-reviewed paper) to describe what you did in task 1a and 1b
Classify the variant below according to the ACMG criteria (https://www.nature.com/articles/gim201530). Provide the evidence used in the classification and why.
- Genotypes:
- Unaffected mother: 0/0
- Unaffected father: 0/0
- Affected child: 0/1
- Phenotype child: Hypotonia, intellectual disability, delayed development
- Gene: HNRNPK
- Variant: NM_031263.4:c.203T>G (p.Leu68Arg)
- Note: paternity and maternity were not confirmed
Complete Task 3: R programming in this orientation: https://github.com/statgenetics/orientation
hint: wget https://raw.githubusercontent.com/statgenetics/orientation/main/analysis/orientation.Rmd to download the exercise file. Data is under the “Data” folder on the github orientation page.