15q21.2CNV Type: Deletion-Duplication
Largest CNV size: 183904 bp
Statistics Box:
Number of Reports: 10
Number of Reports: 10
Summary Information
Summary statement in development
Additional Locus Information
References
Major Reports
Title
Author, Year
Report Class
CNV Type
Structural variation of chromosomes in autism spectrum disorder.
Duplication
An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabili...
Deletion
Both rare and de novo copy number variants are prevalent in agenesis of the corpus callosum but not in cerebellar hypoplasia or polymicrogyria.
Deletion
Paternally inherited cis-regulatory structural variants are associated with autism.
Deletion
De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis.
Deletion
Minor Reports
Title
Author, Year
Report Class
CNV Type
Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism.
Deletion-Duplication
A discovery resource of rare copy number variations in individuals with autism spectrum disorder.
Duplication
Performance of case-control rare copy number variation annotation in classification of autism.
Deletion-Duplication
Copy number variation analysis of patients with intellectual disability from North-West Spain.
Deletion
Cases
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
brandler_18_ASD_discovery_cases
Affected individuals from the Relating Genes with Adolescent and Child Health (REACH) cohort (362 cases from 311 families; 54 multiplex, 243 simplex) and the Simons Simplex 1 (SSC1) cohort (518 cases from simplex quad families)
880
REACH cohort: 285 cases diagnosed with ASD, 43 cases diagnosed with PDD-NOS, 10 cases diagnosed with ADHD, and 24 cases presenting with speech delay, epilepsy, anxiety, or other related developmental disorders that were classified as cases for bioinformatics analyses; Simons Simplex Collection 1 (SSC1) cohort: all 518 cases were diagnosed with ASD
N/A
N/A
21563
3
0
3
engchuan_15_ASD_discovery_cases
Samples from the Autism Genome Project (AGP)
1892
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
N/A
85.78% Male
68272
1
1
2
kaminsky_11_DD/ID/ASD_discovery_cases
Cases from the International Standards for Cytogenomic Arrays (ISCA) consortium
15749
Unexplained developmental delay, intellectual disability, dysmorphic features, multiple congenital anomalies, autism spectrum disorders, or clinical features suggestive of a chromosomal syndrome
NA
NA
221793
2
0
2
lintas_22_ASD/DD/ID_discovery_cases
Female subject with a 15q21.2 microdeletion inherited from a mother presenting with severe anxiety disorder who was referred to the Genetic Counseling Service from Neuropsychiatric Clinics.
1
Case diagnosed with autism spectrum disorder (ADOS-2) and borderline intellectual disability (WAIS-IV) and presenting with delayed language acquistion.
21 yrs.
Female
174412
1
0
1
marshall_08_ASD_discovery_cases
Cohort of ASD families (237 simplex, 189 mulitplex) recruited from the Hospital for Sick Children, McMaster Univ., Memorial Univ., and other sites
427
ASD
183904
0
1
1
prasad_12_ASD_discovery_cases
Unrelated ASD cases recruited from three Canadian sites (Hospital for Sick Children, McMaster University, and Memorial University of Newfoundland); the majority of cases had been previously genotyped with results published in Marshall et al., 2008 and Pinto et al., 2010. 20 cases from initial cohort of 696 were excluded from further analysis (due to CNVs > 5 Mb).
676
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS
NA
82.84% Male
23454
0
1
1
quintela_17_DD/ID_discovery_cases
Galician (NW Spain) patients recruited from the Complexo Hospitalario Universitario de Santiago de Compostela and referred to the Fundacion Publica Galega de Medicina Xenomica for genetic study
573
All participants had a clinical diagnosis of idiopathic intellectual disability (ID) or global developmental delay (DD) with or without another medical condition [e.g. autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), epilepsy, dysmorphic features, and/or congenital anomalies]
Range, 3 months-18 years
60.38% Male
112149
1
0
1
sajan_13_ACC/CBLH/PMG_discovery_cases
Individuals with severe congenital brain malformations [agenesis of the corpus callosum (ACC), cerebellar hypoplasia (CBLH), and/or polymicrogyria (PMG)] and additional neurodevelopmental phenotypes
487
Diagnosis of agenesis of the corpus callosum (ACC), cerebellar hypoplasia (CBLH), and/or polymicrogyria (PMG); additional diagnoses of autism spectrum disorder (ASD), developmental delay (DD), intellectual disability (ID) and/or seizures in some patients
N/A
N/A
93119
1
0
1
sanders_11_ASD_discovery_cases
Autistic probands from the Simons Simplex Collection (SSC). 872 probands in quartet families, 272 probands in trios.
1124
ASD diagnosis: 89.5% autism; 8.5% PDD-NOS, 2% Asperger syndrome. Mean full-scale IQ 85.1 1.5 (mean verbal IQ, 81.9 1.7; mean non-verbal IQ, 88.4 1.4)
Mean, 9.1 yrs.
86.1% Male
84587
1
2
3
wang_18_TS_discovery_cases
Probands from 789 trio families (582 simplex trios, 103 multi-generational trios, and 104 trios with insufficient parental phenotypic data) from TIC Genetics, TAAICG, UTC, and TSGENESEE cohorts
789
Probands diagnosed with Tourette syndrome
N/A
80.57% Male
332557
1
0
1
Controls
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
engchuan_15_ASD_discovery_controls
Platform-matched controls from three large studies: SAGE (Study of Addiction Genetics and Environment), Ontario Colorectal Cancer study, and HABC (Health Aging and Body Composition)
2342
Controls; subjects had no previous psychiatric history
N/A
46.67% Male
197431
0
5
5
kaminsky_11_DD/ID/ASD_discovery_controls
Controls from the International Standards for Cytogenomic Arrays (ISCA) consortium
10118
Controls
NA
NA
NA
NA
NA
NA
krumm_13_ASD_discovery_controls
Unaffected siblings of ASD probands from quad families ascertained as part of the Simons Simplex Collection (SSC); CNVs detected using data from four previously published exome sequencing studies (O'Roak et al., 2011; Iossifov et al., 2012; O'Roak et al., 2012; Sanders et al., 2012)
411
Control (unaffected siblings of ASD probands). Social Responsiveness Scale (SRS) used as a quantitative measure of social deficits
N/A
46.47% Male
803839
0
1
1
marshall_08_ASD_discovery_controls_1
German PopGen project and entries from Database of Genomic Variants
500
Controls
0
0
0
0
marshall_08_ASD_discovery_controls_2
Non-disease controls from Ontario population
1152
Controls
0
0
0
0
prasad_12_ASD_discovery_controls
PDx controls [1000 DNA samples from reportedly healthy donors (50.2% male) from BioServe (Beltsville, MD)] and 4139 in-house controls previously reported in Krawcak et al. 2006, Stewart et al. 2009, and Bierut et al. 2010. CNVs identified in controls were used to define rare ASD-specific CNVs.
5139
Control
NA
NA (PDx controls 50.2% male)
23454
0
0
0
sanders_11_ASD_discovery_controls
Matched siblings of autistic probands from the Simons Simplex Collection (SSC).
872
Controls
Mean, 10.0 yrs.
905624
2
2
4
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
brandler_18_ASD_discovery_cases
N/A
WGS
Illumina HiSeq X10 or HiSeq 2500
ForestSV, Lumpy, Manta, Mobster, SV2
PCR, array SNP
engchuan_15_ASD_discovery_cases
Caucasian
Solid phase hybridization
Illumina 1M
None
kaminsky_11_DD/ID/ASD_discovery_cases
NA
aCGH
Agilent 44K, Agilent 105K
Feature Extraction, DNA Analytics
FISH, qPCR, MLPA, aCGH, standard G-banded chromosome analysis
lintas_22_ASD/DD/ID_discovery_cases
Italy
aCGH
OGT CytoSure 8X60K ISCA v2
NA
NA
None
marshall_08_ASD_discovery_cases
90% European, 4.5% European-mixed, 4.5% Asian, 0.07% African
Array SNP, karotyping
Affymetrix 500K
dChip, CNAG, GEMCA
qPCR, qmPCR
prasad_12_ASD_discovery_cases
Canada
aCGH
Agilent 1M
ADM-2, DNAcopy (R Bioconductor)
DNA Analytics v4.0.85 (Agilent), DNAcopy
None
quintela_17_DD/ID_discovery_cases
North West Spain
Array SNP
Affymetrix Cytogenetics Whole-Genome 2M SNP array, Affymetrix CytoScan HD
Affymetrix ChAS v.1.2.2
None
sajan_13_ACC/CBLH/PMG_discovery_cases
81.31% Caucasian
Solid phase hybridization
Illumina InfiniumII HumanHap610
PennCNV
qPCR
sanders_11_ASD_discovery_cases
White non-Hispanic, 74.5%; mixed, 9.3%, Asian, 4.3%, White Hispanic, 4.0%, African-American, 3.8%; other, 4.2&
Solid phase hybridization
Illumina 1M v1, Illumina 1M v3
PennCNV, QuantiSNP, GNOSIS
wang_18_TS_discovery_cases
N/A
WES
Agilent SureSelect v1.1, Nimblegen EZ v2, Nimblegen EZ v3, IDT xGen
CoNIFER
qPCR
Controls
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
engchuan_15_ASD_discovery_controls
Caucasian
Solid phase hybridization
Illumina 1M
None
kaminsky_11_DD/ID/ASD_discovery_controls
NA
aCGH
Agilent 44K, Agilent 105K
Feature Extraction, DNA Analytics
krumm_13_ASD_discovery_controls
N/A
WES
Whole exome sequencing platforms used in four recent publications (O'Roak et al., 2011; Sanders et al., 2012; O'Roak et al., 2012, and Iossifov et al., 2012)
DNACopy, CGHCall
CoNIFER
None
marshall_08_ASD_discovery_controls_1
European
Array SNP, karotyping
Affymetrix 500K
dChip, CNAG, GEMCA
marshall_08_ASD_discovery_controls_2
European
Array SNP, karotyping
Affymetrix 500K
dChip, CNAG, GEMCA
prasad_12_ASD_discovery_controls
NA
aCGH
Agilent 1M
ADM-2, DNAcopy (R Bioconductor)
DNA Analytics v4.0.85 (Agilent), DNAcopy
sanders_11_ASD_discovery_controls
Solid phase hybridization
Illumina 1M v1 or Illumina 1M v3
PennCNV, QuantiSNP, GNOSIS
Cases
Patient ID
Author, Year
Age
Gender
Primary Diagnosis
Clinical Profile
Cognitive Profile
CNV Start
CNV End
CNV Size
Genome Build
Type Method
Validation
brandler_18_ASD_discovery_cases-case14-591
N/A
F
ASD
Case from REACH cohort
51972489
51994052
21564
GRCh38
Deletion
Yes
brandler_18_ASD_discovery_cases-caseREACH000319
N/A
M
ASD
Case from REACH cohort
51972569
51989334
16766
GRCh38
Deletion
Yes
brandler_18_ASD_discovery_cases-caseREACH000322
N/A
M
ASD
Case from REACH cohort
51972569
51989334
16766
GRCh38
Deletion
Yes
engchuan_15_ASD_discovery_cases-case14415_5240
N/A
N/A
ASD
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
50742924
50811196
68273
GRCh38
Duplication
No
engchuan_15_ASD_discovery_cases-case3205_3
N/A
N/A
ASD
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
50789374
50822889
33516
GRCh38
Deletion
No
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00000623
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
50756382
50978175
221794
GRCh38
Deletion
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001993
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
52005056
52098273
93218
GRCh38
Deletion
Yes
lintas_22_ASD/DD/ID_discovery_cases-case1
21 yrs.
F
ASD, developmental delay, and intellectual disability
Birth/neonatal history: born prematurely at 29 weeks gestation showing a severe degree of cerebral suffering; birth weight 0.750 kg, birth length 31 cm; hospitalized in intensive care for about 4 months; atrial and interventricular septal defect detected at birth and surgically repaired. Developmental milestones: delayed language acquisition. Motor and musculoskeletal evaluation: involuntary movements such as motor tics. Behavioral/psychiatric evaluation: case diagnosed with autism spectrum disorder (ASD) (ADOS-2 language and communication score 1, social interaction score 7, total score 8); impaired attention, deficit in self-regulation of emotional response with agitation when frustrated, deficits in social skills, tendency to isolate from peers, poor communication with socio-pragmatic deficits, insistence on sameness with complex patterns of routinized and ritualistic behaviors, restrictive interests and activities, stereotypies, marked asthenia with excessive daytime sleepiness, noise hypersensitivity; MMPI-2 clinical profile highlighted a mildly depressed mood, social introversion, anxious traits, obessive-compulsive behaviors, and generalized distress and difficulty in interpreting reality with a tendency to attribute personal meanings to neutral events. Epilepsy/seizures: suspected epileptic seizure at 10 years with no clear epiieptogenic etiology on EEG. Additional medical history: bronchodysplasia due to severe prematurity, migraine with aura, vascular malformation in the right lower limb, arteriovenous fistula, gastrointestinal problems with constipation. Dysmorphic features: none reported. Family history: first and only child of apparently healthy and unrelated parents, although her mother was affected by severe anxiety disorder.
Borderline intellectual disability (WAIS-IV full scale IQ 75; verbal comprehension IQ 84, visuo-perceptual reasoning IQ 90, working memory IQ 72, visuo-motor speed IQ 72); delayed acquisition of calculation and arithmetic skills (learning disorder), dyspraxia, impaired executive functions (poor performance on Trail-making test, Tower of London, and phonological fluency).
50097720
50272131
174412
GRCh38
Deletion
No
marshall_08_ASD_discovery_cases-SK0300-003
NA
M
ASD
NA
NA
50503638
50687541
183904
GRCh38
Duplication
Yes
prasad_12_ASD_discovery_cases-case113501L
NA
M
ASD
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS. Novel CNV
49146071
49169524
23454
Unknown
Duplication
No
quintela_17_DD/ID_discovery_cases-caseID_258
15 yrs.
M
Intellectual disability
Additional clinical information N/A
Mild intellectual disability
52014939
52127087
112149
GRCh38
Deletion
No
sajan_13_ACC/CBLH/PMG_discovery_cases-caseLR03-260
N/A
N/A
PMG
Diagnosis of polymicrogyria (PMG).
52099709
52192827
93119
GRCh38
Deletion
Yes
sanders_11_ASD_discovery_cases-11099.p1
11.4
M
Autism
NA
Full-scale IQ, 83; non-verbal IQ, 89; verbal IQ, 77
52709341
52733495
24155
GRCh38
Duplication
No
sanders_11_ASD_discovery_cases-11860.p1
6
M
Autism
NA
Full-scale IQ, 86; non-verbal IQ, 95; verbal IQ, 75
52689677
52697350
7674
GRCh38
Deletion
No
sanders_11_ASD_discovery_cases-12327.p1
14.6
M
Autism
NA
Full-scale IQ, 97; non-verbal IQ, 108; verbal IQ, 83
52530644
52615231
84588
GRCh38
Duplication
No
wang_18_TS_discovery_cases-case25094.p1
N/A
N/A
Tourette syndrome
Tourette syndrome proband from phase 1 cohort; no additional clinical information available
49235809
49568365
332557
GRCh38
Deletion
Yes
Controls
Patient ID
Author, Year
Age
Gender
Primary Diagnosis
Clinical Profile
Cognitive Profile
CNV Start
CNV End
CNV Size
Genome Build
Type Method
Validation
engchuan_15_ASD_discovery_controls-controlB916582_1007854385
N/A
N/A
Control
No previous psychiatric history
50675526
50770936
95411
GRCh38
Duplication
No
engchuan_15_ASD_discovery_controls-controlHABC_900025_900025
N/A
N/A
Control
No previous psychiatric history
51424428
51499362
74935
GRCh38
Duplication
No
engchuan_15_ASD_discovery_controls-controlHABC_900564_900564
N/A
N/A
Control
No previous psychiatric history
52706065
52746291
40227
GRCh38
Duplication
No
engchuan_15_ASD_discovery_controls-controlHABC_901040_901040
N/A
N/A
Control
No previous psychiatric history
50510070
50707501
197432
GRCh38
Duplication
No
engchuan_15_ASD_discovery_controls-controlHABC_902690_902690
N/A
N/A
Control
No previous psychiatric history
50593779
50625910
32132
GRCh38
Duplication
No
krumm_13_ASD_discovery_controls-control13216.s1
N/A
M
Control
Unaffected sibling from SSC quad family 13216. SRS score of 50.
50439073
51242912
803840
GRCh38
Duplication
No (not tested)
sanders_11_ASD_discovery_controls-11316.s1
13.3
F
Control (matched sibling)
NA
NA
51350687
51354172
3486
GRCh38
Deletion
No
sanders_11_ASD_discovery_controls-11860.s1
14.1
M
Control (matched sibling)
NA
NA
52689677
52697350
7674
GRCh38
Deletion
No
sanders_11_ASD_discovery_controls-12327.s1
16.3
F
Control (matched sibling)
NA
NA
52560413
52615231
54819
GRCh38
Duplication
No
sanders_11_ASD_discovery_controls-13216.s1
6
M
Control (matched sibling)
NA
NA
50437077
51342701
905625
GRCh38
Duplication
No
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
brandler_18_ASD_discovery_cases-case14-591
PCR or SNP data validation
Paternal
MAPK6
brandler_18_ASD_discovery_cases-caseREACH000319
PCR or SNP data validation
Paternal
MAPK6
brandler_18_ASD_discovery_cases-caseREACH000322
PCR or SNP data validation
Paternal
MAPK6
engchuan_15_ASD_discovery_cases-case14415_5240
Unknown
SPPL2A
engchuan_15_ASD_discovery_cases-case3205_3
Unknown
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00000623
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
DCAF13P3,SPPL2A,AP4E1
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001993
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
MAPK6-DT,MAPK6
lintas_22_ASD/DD/ID_discovery_cases-case1
Maternal
ATP8B4,HDC,RN7SL494P,SLC27A2
marshall_08_ASD_discovery_cases-SK0300-003
qPCR, qmPCR
Unknown
NA
NA
USP50,USP8,TRPM7
prasad_12_ASD_discovery_cases-case113501L
Unknown
Unknown
Unknown
TNFAIP8L3
quintela_17_DD/ID_discovery_cases-caseID_258
Unknown
Unknown
MAPK6-DT,BCL2L10,MAPK6,GNB5
sajan_13_ACC/CBLH/PMG_discovery_cases-caseLR03-260
qPCR
Unknown
Unknown
Unknown
BCL2L10,CERNA1,MYO5C,GNB5
sanders_11_ASD_discovery_cases-11099.p1
Maternal
Simplex (quad-proband matched)
Segregated
FAM214A
sanders_11_ASD_discovery_cases-11860.p1
Paternal
Simplex (quad-proband matched)
Not segregated
FAM214A
sanders_11_ASD_discovery_cases-12327.p1
Maternal
Simplex (quad-proband matched)
Not segregated
ARPP19,FAM214A
wang_18_TS_discovery_cases-case25094.p1
qPCR
De novo
FGF7,FAM227B,GALK2
Controls
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
engchuan_15_ASD_discovery_controls-controlB916582_1007854385
Unknown
RN7SL354P,TRPM7,SPPL2A
engchuan_15_ASD_discovery_controls-controlHABC_900025_900025
Unknown
DMXL2
engchuan_15_ASD_discovery_controls-controlHABC_900564_900564
Unknown
FAM214A
engchuan_15_ASD_discovery_controls-controlHABC_901040_901040
Unknown
RN7SL354P,USP50,USP8,TRPM7,SPPL2A
engchuan_15_ASD_discovery_controls-controlHABC_902690_902690
Unknown
TRPM7
krumm_13_ASD_discovery_controls-control13216.s1
Paternal
Simplex
RNA5SP395,RN7SL354P,DCAF13P3,MIR4713,USP50,TNFAIP8L3,USP8,TRPM7,SPPL2A,AP4E1,MIR4713HG,CYP19A1
sanders_11_ASD_discovery_controls-11316.s1
Paternal
Simplex (quad)
NA
GLDN
sanders_11_ASD_discovery_controls-11860.s1
Paternal
Simplex (quad)
NA
FAM214A
sanders_11_ASD_discovery_controls-12327.s1
Maternal
Simplex (quad)
NA
ARPP19,FAM214A
sanders_11_ASD_discovery_controls-13216.s1
Paternal
Simplex (quad)
NA
RNA5SP395,RN7SL354P,DCAF13P3,MIR4713,MIR7973-2,MIR7973-1,USP50,TNFAIP8L3,USP8,TRPM7,SPPL2A,AP4E1,MIR4713HG,CYP19A1,GLDN
No Animal Model Data Available