Scalable application for prioritising clinically relevant variants from WGS/WES/Panel studies built using Apache Spark.
This software will extract annotated variants to text file that fall into these categories:
- Dominant inheritance
- Recessive inheritance
- Compound Heterozygous inheritance
- De Novo (trio only)
- Uniparental disomy (trio only)
Perform variant calling, filtering and annotation using the GermlineEnrichment pipeline.
Run variant prioritise workflow
/share/apps/jre-distros/jre1.8.0_131/bin/java \
-Djava.io.tmpdir=/state/partition1/tmpdir \
-Xmx48g \
-jar /data/diagnostics/apps/VariantReporterSpark/VariantReporterSpark-1.3.2/VariantReporterSpark.jar \
-V calls.vcf \
-P pedigree.ped \
-T <threads> \
-N
Variants are passed through a series of filters as shown in the flowchart and described below.
Identifies variant sites for downstream analysis
- Pass all context filters (Quality, QD, FS, MQ, MQRankSum, ReadPosRankSum, InbreedingCoeff)
- Has functional annotation
- Non reference in one or more samples
- Less than 1% population allele frequency (Gnomad) for one or more alternative alleles
Identifies genotypes for downstream analysis
- Must pass genotype filters (DP >10, GQ > 20)
- Cannot be homozygous for the reference allele
- Cannot be no call (insufficient data to call genotype)
- Autosomal
- Heterozygous
- Cohort allele count < 4
- gnomAD (Exome) allele frequency < 0.1%
- gnomAD (Genome) allele frequency < 0.75%
- X-Female
- As autosomal
- X/Y-Male
- Homozygous (hemizygous)
- Cohort allele count < 6
- gnomAD (Exome) allele frequency < 0.1%
- gnomAD (Genome) allele frequency < 0.75%
- Autosomal
- Homozygous for alternative allele
- Cohort allele count < 4
- gnomAD (Exome) allele frequency < 1%
- gnomAD (Genome) allele frequency < 1%
- X-Female
- Homozygous for alternative allele
- Cohort allele count < 8
- gnomAD (Exome) allele frequency < 1%
- gnomAD (Genome) allele frequency < 1%
- Autosomal or X-Female
- Heterozygous
- gnomAD (Exome) allele frequency < 1%
- gnomAD (Genome) allele frequency < 1%
- Two or more variants per gene
- Any chromosome
- Both parents are homozygous reference
- Cohort allele count < 4
- gnomAD (Exome) allele frequency < 0.1%
- gnomAD (Genome) allele frequency < 0.75%
- Autosomal
- Homozygous for alternative allele
- Mother is heterozygous and father is homozygous reference OR mother is homozygous reference and father is heterozygous
- gnomAD (Exome) allele frequency < 1%
- gnomAD (Genome) allele frequency < 1%
- X-Female
- Homozygous for alternative allele
- Mother is heterozygous and father is homozygous reference OR mother is homozygous reference and father is homozygous (hemizygous) alternative
- gnomAD (Exome) allele frequency < 1%
- gnomAD (Genome) allele frequency < 1%
Variant has consequence on one or more transcripts
- frameshift_variant
- incomplete_terminal_codon_variant
- inframe_deletion
- inframe_insertion
- initiator_codon_variant
- missense_variant
- splice_acceptor_variant
- splice_donor_variant
- splice_region_variant
- stop_gained
- stop_lost
- synonymous_variant
- transcript_ablation
- transcript_amplification