12q21.33CNV Type: Deletion-Duplication
Largest CNV size: 434827 bp
Statistics Box:
Number of Reports: 9
Number of Reports: 9
Summary Information
Summary statement in development
Additional Locus Information
References
Major Reports
Title
Author, Year
Report Class
CNV Type
An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabili...
Duplication
Excess of rare, inherited truncating mutations in autism.
Deletion-Duplication
Minor Reports
Title
Author, Year
Report Class
CNV Type
Rare structural variation of synapse and neurotransmission genes in autism.
Deletion
Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism.
Deletion-Duplication
Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay.
Unknown
A discovery resource of rare copy number variations in individuals with autism spectrum disorder.
Deletion
Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.
Deletion
Global increases in both common and rare copy number load associated with autism.
Duplication
Identification of small exonic CNV from whole-exome sequence data and application to autism spectrum disorder.
Deletion
Cases
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
al-murrani_12_DD_discovery_cases
Second child born to non-consanguineous European couple with normal langauge development
1
Speech delay, mild motor delay, and behavioral problems resulting from communication difficulties
3 yrs.
Male
232212
1
gai_11_ASD_discovery_cases
Discovery case samples derived from AGRE set 4 (most recent patient recruitment)
631
Idiopathic autism; cases designated as 'spectrum' and 'not quite autism' excluded, as were cases with known genetic syndromes or other non-idiopathic causes
352518
1
0
1
girirajan_13a_ASD_discovery_cases
1979 simplex cases from the Simons Simplex Collection (SSC), 579 multiplex cases from AGRE.
2588
Diagnosis of ASD based on meeting criteria on the Autism Diagnostic Observation Schedule (ADOS) and on the Autism Diagnostic Interview, Revised (ADI-R)
NA
NA
359000
1
0
1
girirajan_13b_ASD_discovery_cases
Children with autism ascertained from the Childhood Autism Risks from Genetics and Environment (CHARGE) study conducted through the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute at UC-Davis after passing QC criteria (274 initial cases)
243
Diagnosis of autism confirmed by ADOS and ADI-R. Exclusion criteria: children with developmental delay but lacking symptoms and autism, as well as children with ASD as defined by the CHARGE protocol
N/A
N/A
404542
0
1
1
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
1054299
0
2
2
krumm_15_ASD_discovery_cases
Probands from the Simons Simplex Collection
2377
Diagnosis of ASD
N/A
N/A
29752
1
1
2
poultney_13_ASD_discovery_cases
ASD cases of European ancestry from AGRE retained after filtering (original cohort size of 432 cases)
299
Cases diagnosed with ASD
N/A
79.86% Male (before filtering)
225035
1
0
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
55558
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
434827
1
1
2
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
250159
1
1
2
girirajan_13b_ASD_discovery_controls
Controls ascertained from the Childhood Autism Risks from Genetics and Environment (CHARGE) study conducted through the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute at UC-Davis after passing QC criteria (242 initial controls)
223
Control
N/A
N/A
0
0
0
0
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_15_ASD_discovery_controls
Unaffected siblings from quad families from the Simons Simplex Collection
1786
Control
N/A
N/A
0
0
0
0
poultney_13_ASD_discovery_controls
Controls matched for European ancestry from NIMH and CEPH retained after filtering (original cohort size of 379 controls)
260
Control
N/A
47.49% Male (before filtering)
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)
55558
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.
446446
2
2
4
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
al-murrani_12_DD_discovery_cases
European
Array SNP
Affymetrix 2.7M
Affymetrix ChAS v.1.0.1
None
gai_11_ASD_discovery_cases
European
Solid phase hybridization
Illumina Infinium II HumanHap550 BeadChip
BeadStudio 3.0
None
girirajan_13a_ASD_discovery_cases
NA
aCGH
Custom microarray with a high density of probes targeted to 1,367 regions with a susceptible genomic architecture
ADM-2
Agilent Genomic Workbench
None
girirajan_13b_ASD_discovery_cases
133 European, 57 Hispanic, 27 Mixed Race, 20 Asian, 6 African-American
aCGH
Roche NimbleGen custom targeted hotspot array comprised of 135,000 probes with higher density probe coverage in genomic hotspots (regions flanked by segmental duplications)
DNA Copy Number v1.6
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
krumm_15_ASD_discovery_cases
N/A
WES
CoNIFER, XHMM
Solid phase hybridization (Illumina 1M, 1 M Duo, or Omni 2.5)
poultney_13_ASD_discovery_cases
European
WES
Agilent SureSelect Human All Exon v.2
XHMM
None
prasad_12_ASD_discovery_cases
Canada
aCGH
Agilent 1M
ADM-2, DNAcopy (R Bioconductor)
DNA Analytics v4.0.85 (Agilent), DNAcopy
None
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
Controls
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
engchuan_15_ASD_discovery_controls
Caucasian
Solid phase hybridization
Illumina 1M
None
girirajan_13b_ASD_discovery_controls
116 European, 70 Hispanic, 27 Mixed Race, 7 Asian, 3 African-American
aCGH
Roche NimbleGen custom targeted hotspot array comprised of 135,000 probes with higher density probe coverage in genomic hotspots (regions flanked by segmental duplications)
DNA Copy Number v1.6
kaminsky_11_DD/ID/ASD_discovery_controls
NA
aCGH
Agilent 44K, Agilent 105K
Feature Extraction, DNA Analytics
krumm_15_ASD_discovery_controls
N/A
WES
CoNIFER, XHMM
None
poultney_13_ASD_discovery_controls
European
WES
Agilent SureSelect Human All Exon v.2
XHMM
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
al-murrani_12_DD_discovery_cases-case1
3 yrs.
M
Speech delay
Case referred to genetic service for opinion regarding an abnormal molecular karyotpye result. Birth/neonatal history: uneventful perinatal history, born at term. Developmental milestones: mild motor delay (walking at around 18-20 months), speech late to develop; able to pronounce six words at age of 2.5 years. Language and communication evaluation: uses up to 3 words in sentences; speech difficult to understand. Motor and musculoskeletal evaluation: speech therapist notd presence of reduced tone of orofacial musculature with associated tendency to dribble. Behavioral/psychiatric evaluation: behavioral problems resulting from communication difficulties. Auditory evaluation: normal hearing. Dysmorphic features: none. Growth parameters: normal growth. Family history: second child born to non-consanguineous European couple with normal language development; mother not affected by any learning or speech difficulties; 5-year-old brother with normal language development for his age, but reported to have difficulties in comprehension and following instructions. Mother and brother both carry 7q35/CNTNAP2 deletion.
NA
90504128
90736340
232213
GRCh38
Unknown
No
gai_11_ASD_discovery_cases-AU1081301
Autism
89833922
90186439
352518
Unknown
Deletion
No
girirajan_13a_ASD_discovery_cases-AU1081301
N/A
N/A
ASD
Diagnosis of ASD based on meeting criteria on the Autism Diagnostic Observation Schedule (ADOS) and on the Autism Diagnostic Interview, Revised (ADI-R)
N/A
90912092
91272092
360001
GRCh38
Deletion
No
girirajan_13b_ASD_discovery_cases-9105102949
N/A
N/A
Autism
Diagnosis of autism confirmed by ADOS and ADI-R. Ethnicity: Mixed Race
N/A
90239574
90644116
404543
GRCh38
Duplication
No
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00004803
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
90195589
91249888
1054300
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00004984
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
90197297
91239004
1041708
GRCh38
Duplication
Yes
krumm_15_ASD_discovery_cases-case14090.p1
N/A
Male
ASD
Proband from the Simons Simplex Collection (SSC). Family type: Quad
89421152
89425379
4228
GRCh38
Deletion
Yes
krumm_15_ASD_discovery_cases-case14340.p1
N/A
Male
ASD
Proband from the Simons Simplex Collection (SSC). Family type: Trio
90948510
90978262
29753
GRCh38
Duplication
Yes
poultney_13_ASD_discovery_cases-case05HI3800A
N/A
M
ASD
ASD case from AGRE (AGRE ID AU1081301; NDAR ID NDAR_INVPU716GCV)
90953520
91178554
225035
GRCh38
Deletion
No
prasad_12_ASD_discovery_cases-case100580L
NA
M
ASD
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS. CNV identified by previous SNP microarray study
89654147
89709704
55558
Unknown
Deletion
No
sanders_11_ASD_discovery_cases-12103.p1
6.6
M
Autism
NA
Full-scale IQ, 38; non-verbal IQ, 44; verbal IQ, 31
90676628
90714285
37658
GRCh38
Deletion
No
sanders_11_ASD_discovery_cases-12691.p1
10.9
F
Autism
NA
Full-scale IQ, 34; non-verbal IQ, 32; verbal IQ, 39
90225067
90659894
434828
GRCh38
Duplication
No
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-controlB492772_1007875828
N/A
N/A
Control
No previous psychiatric history
90722713
90972872
250160
GRCh38
Deletion
No
engchuan_15_ASD_discovery_controls-controlHABC_901256_901256
N/A
N/A
Control
No previous psychiatric history
90844143
90897907
53765
GRCh38
Duplication
No
sanders_11_ASD_discovery_controls-11831.s1
7.5
F
Control (matched sibling)
NA
NA
88615098
88742917
127820
GRCh38
Duplication
No
sanders_11_ASD_discovery_controls-12113.s1
6.5
M
Control (matched sibling)
NA
NA
90676628
90719504
42877
GRCh38
Deletion
No
sanders_11_ASD_discovery_controls-12198.s1
11.3
M
Control (matched sibling)
NA
NA
90676628
90714285
37658
GRCh38
Deletion
No
sanders_11_ASD_discovery_controls-12691.s1
23.8
M
Control (matched sibling)
NA
NA
90225067
90671513
446447
GRCh38
Duplication
No
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
al-murrani_12_DD_discovery_cases-case1
Maternal
Simplex
Segregated
gai_11_ASD_discovery_cases-AU1081301
Inherited
C12orf12, EPYC, KERA, LUM, DCN
girirajan_13a_ASD_discovery_cases-AU1081301
Unknown
Multiplex
Unknown
KERA,CCER1,LINC00615,LUM,DCN,EPYC
girirajan_13b_ASD_discovery_cases-9105102949
Unknown
Unknown
Unknown
LINC02392
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00004803
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Paternal
Unknown
Unknown
KERA,LINC02392,CCER1,LINC00615,LUM,DCN,EPYC
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00004984
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Maternal
Unknown
Unknown
KERA,LINC02392,CCER1,LINC00615,LUM,DCN,EPYC
krumm_15_ASD_discovery_cases-case14090.p1
Omni2.5-4v1
Paternal
Simplex
Segregated
POC1B
krumm_15_ASD_discovery_cases-case14340.p1
Omni2.5-4v1
Maternal
Simplex
Segregated
CCER1,LINC00615,EPYC
poultney_13_ASD_discovery_cases-case05HI3800A
Unknown
Unknown (likely multiplex/AGRE)
Unknown
KERA,CCER1,LUM,DCN,EPYC
prasad_12_ASD_discovery_cases-case100580L
Unknown
Unknown
Unknown
0 genes
sanders_11_ASD_discovery_cases-12103.p1
Unknown
Simplex (quad-proband unmatched)
Unknown
sanders_11_ASD_discovery_cases-12691.p1
Maternal
Simplex (quad-proband matched)
Not segregated
LINC02392
Controls
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
engchuan_15_ASD_discovery_controls-controlB492772_1007875828
Unknown
CCER1,LINC00615,EPYC
engchuan_15_ASD_discovery_controls-controlHABC_901256_901256
Unknown
sanders_11_ASD_discovery_controls-11831.s1
Paternal
Simplex (quad)
NA
sanders_11_ASD_discovery_controls-12113.s1
Unknown
Simplex (quad)
NA
sanders_11_ASD_discovery_controls-12198.s1
Unknown
Simplex (quad)
NA
sanders_11_ASD_discovery_controls-12691.s1
Maternal
Simplex (quad)
NA
LINC02392
No Animal Model Data Available