Examples
This section shows how SvAnna prioritizes various structural variant classes. The resulting HTML reports contain graphics that are reported in the supplement of SvAnna paper.
The examples work with variants stored in examples.vcf file. The VCF file is stored in SvAnna GitHub repository.
Use the run_examples.sh script to generate HTML reports for all cases described below. Note that you must enter
the paths to SvAnna JAR file, data directory, and the examples.vcf
into the script before running.
Single exon deletion
A deletion of 6.93 kb (chr17:31,150,798-31,157,725del
) affecting NF1 that was assigned a PSV score of 124.98.
The deletion affects exon 2 of several NF1 transcripts.
Pathogenic variants in NF1 are associated with neurofibromatosis type 1 (OMIM:162200
).
The phenotypic features curated for the proband UAB-1
were:
HP:0007565
Multiple cafe-au-lait spotsHP:0009732
Plexiform neurofibromaHP:0009735
Spinal neurofibromasHP:0009736
Tibial pseudarthrosis
Data were curated from a published case report in Decoding NF1 Intragenic Copy-Number Variations.
Command
$ java -jar svanna-cli.jar prioritize -d path/to/svanna-data --vcf example.vcf --term HP:0007565 --term HP:0009732 --term HP:0009735 --term HP:0009736
Deletion of multiple exons
A deletion of 10.26 kb (chr17:43,100,079-43,110,335del
) affecting BRCA1 that was assigned a PSV score of 272.91.
The deletion affects three BRCA1 exons. Pathogenic variants in BRCA1 are associated with
Breast-ovarian cancer, familial, 1 (OMIM:604370
).
The phenotypic feature curated for this case was:
HP:0003002
Breast carcinoma
Data were curated from a published case report The first case report of a large deletion of the BRCA1 gene in Croatia.
Command
$ java -jar svanna-cli.jar prioritize -d path/to/svanna-data --vcf example.vcf --term HP:0003002
Deletion of multiple genes
Deletion of 481.73 kb (chr2:109,923,337-110,405,062del
) affecting MALL, NPHP1, and MTLN
that was assigned a PSV score of 16.41.
Pathogenic variants in NPHP1 are associated with Joubert syndrome 4 (OMIM:609583
).
The phenotypic features curated for this case were:
HP:0003774
Stage 5 chronic kidney diseaseHP:0001320
Cerebellar vermis hypoplasiaHP:0002078
Truncal ataxiaHP:0000618
BlindnessHP:0000508
PtosisHP:0002419
Molar tooth sign on MRIHP:0011933
Elongated superior cerebellar peduncleHP:0002070
Limb ataxiaHP:0000543
Optic disc pallorHP:0000589
Coloboma
Data were curated from a published case report Whole-exome sequencing and digital PCR identified a novel compound heterozygous mutation in the NPHP1 gene in a case of Joubert syndrome and related disorders.
Command
$ java -jar svanna-cli.jar prioritize -d path/to/svanna-data --vcf example.vcf --term HP:0003774 --term HP:0001320 --term HP:0002078 --term HP:0000618 --term HP:0000508 --term HP:0002419 --term HP:0011933 --term HP:0002070 --term HP:0000543 --term HP:0000589
Duplication of coding sequence
Duplication of 36 bp (chr13:72835296-72835332dup
) affecting PIBF1 that was assigned a PSV score of 3.29.
Pathogenic variants in PIBF1 are associated with Joubert syndrome 33 (OMIM:617767
).
The phenotypic features curated for this case were:
HP:0032417
Periglomerular fibrosisHP:0000076
Vesicoureteral refluxHP:0002079
Hypoplasia of the corpus callosumHP:0001541
AscitesHP:0000540
HypermetropiaHP:0011968
Feeding difficultiesHP:0001250
SeizureHP:0000490
Deeply set eyeHP:0001263
Global developmental delayHP:0001284
AreflexiaHP:0002240
HepatomegalyHP:0001290
Generalized hypotoniaHP:0031200
Hyaline castsHP:0011800
Midface retrusionHP:0000090
NephronophthisisHP:0000092
Renal tubular atrophyHP:0001919
Acute kidney injuryHP:0012650
Perisylvian polymicrogyriaHP:0002419
Molar tooth sign on MRIHP:0002119
VentriculomegalyHP:0000105
Enlarged kidney
Data were curated from a published case report A biallelic 36-bp insertion in PIBF1 is associated with Joubert syndrome
Command
$ java -jar svanna-cli.jar prioritize -d path/to/svanna-data --vcf example.vcf --term HP:0032417 --term HP:0000076 --term HP:0002079 --term HP:0001541 --term HP:0000540 --term HP:0011968 --term HP:0001250 --term HP:0000490 --term HP:0001263 --term HP:0001284 --term HP:0002240 --term HP:0001290 --term HP:0031200 --term HP:0011800 --term HP:0000090 --term HP:0000092 --term HP:0001919 --term HP:0012650 --term HP:0002419 --term HP:0002119 --term HP:0000105
Multigene inversion
Inversion of ~12.23 kb (inv(chr3)(9725702; 9737931)
) that disrupts the coding sequence of BRPF1 was assigned
PSV score of 8.01.
Pathogenic variants in BRPF1 are associated with Intellectual developmental disorder with dysmorphic facies and ptosis OMIM:617333
.
The phenotypic features curated for this case were:
HP:0000316
HypertelorismHP:0000494
Downslanted palpebral fissuresHP:0000431
Wide nasal bridgeHP:0000286
EpicanthusHP:0000311
Round faceHP:0012368
Flat faceHP:0000486
StrabismusHP:0000508
PtosisHP:0002949
Fused cervical vertebraeHP:0002194
Delayed gross motor developmentHP:0000750
Delayed speech and language developmentHP:0002342
Intellectual disability, moderateHP:0011150
Myoclonic absence seizureHP:0002069
Bilateral tonic-clonic seizureHP:0001252
Hypotonia
Data were curated from a published case report Pathogenic 12-kb copy-neutral inversion in syndromic intellectual disability identified by high-fidelity long-read sequencing
Command
$ java -jar svanna-cli.jar prioritize -d path/to/svanna-data --vcf example.vcf --term HP:0000286 --term HP:0002069 --term HP:0000494 --term HP:0002342 --term HP:0000486 --term HP:0000750 --term HP:0000431 --term HP:0001252 --term HP:0002194 --term HP:0012368 --term HP:0011150 --term HP:0002949 --term HP:0000508 --term HP:0000316 --term HP:0000311
Deletion affecting transcription start site
Deletion of ∼1.57 kb (chrX:64,205,190-64,206,761del
) affecting transcription start site of AMER1 was assigned
PSV score of 9.05.
Pathogenic variants in AMER1 are associated with Osteopathia striata with cranial sclerosis (OMIM:300373
).
The phenotypic features curated for this case were:
HP:0001561
PolyhydramniosHP:0002684
Thickened calvariaHP:0000256
MacrocephalyHP:0000316
HypertelorismHP:0031367
Metaphyseal striationsHP:0002744
Bilateral cleft lip and palateHP:0002781
Upper airway obstructionHP:0001004
LymphedemaHP:0000750
Delayed speech and language development
Data were curated from a published case report Deletion of Exon 1 in AMER1 in Osteopathia Striata with Cranial Sclerosis.
Command
$ java -jar svanna-cli.jar prioritize -d path/to/svanna-data --vcf example.vcf --term HP:0001561 --term HP:0000750 --term HP:0002684 --term HP:0002781 --term HP:0000316 --term HP:0031367 --term HP:0002744 --term HP:0000256 --term HP:0001004
Deletion affecting promoter region
A deletion of 13 bp (chr12:6,124,705-6,124,718del
) located in the core promoter region of VWF was assigned PSV score of
47.26.
In the original publication, the deletion was shown to lead to aberrant binding of Ets transcription factors to the site of the deletion (30 bp upstream of ENST00000261405.10) and thereby reduce VWF expression.
Pathogenic variants in VWF are associated with von Willebrand disease (OMIM:193400
).
The phenotypic features curated for this case were:
HP:0011890
Prolonged bleeding following procedureHP:0000978
Bruising susceptibilityHP:0012147
Reduced quantity of Von Willebrand factor
Data were curated from a published case report Functional characterization of a 13-bp deletion (c.-1522_-1510del13) in the promoter of the von Willebrand factor gene in type 1 von Willebrand disease.
Command
$ java -jar svanna-cli.jar prioritize -d path/to/svanna-data --vcf example.vcf --term HP:0011890 --term HP:0000978 --term HP:0012147
Translocation disrupting a gene sequence
A translocation (t(chr3:11,007,014; chr4:139,383,334)
) affecting SLC6A1 was assigned PSV score of 4.51.
Pathogenic variants in SLC6A1 are associated with Myoclonic-atonic epilepsy (OMIM:616421
).
The phenotypic features curated for this case were:
HP:0000252
MicrocephalyHP:0000446
Narrow nasal bridgeHP:0000272
Malar flatteningHP:0000219
Thin upper lip vermilionHP:0000179
Thick lower lip vermilionHP:0002650
ScoliosisHP:0002987
Elbow flexion contractureHP:0006380
Knee flexion contractureHP:0001250
SeizureHP:0001263
Global developmental delayHP:0001276
Hypertonia
Data were curated from a published case report Phenotypic consequences of gene disruption by a balanced de novo translocation involving SLC6A1 and NAA15
Command
$ java -jar svanna-cli.jar prioritize -d path/to/svanna-data --vcf example.vcf --term HP:0000252 --term HP:0000446 --term HP:0000272 --term HP:0000219 --term HP:0000179 --term HP:0002650 --term HP:0002987 --term HP:0006380 --term HP:0001250 --term HP:0001263 --term HP:0001263 --term HP:0001276