21q22.11-q22.12CNV Type: Duplication
Largest CNV size: 184418 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
Rare structural variation of synapse and neurotransmission genes in autism.
Duplication
An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabili...
Duplication
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.
Duplication
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.
Duplication
Transmission disequilibrium of small CNVs in simplex autism.
Duplication
Both rare and de novo copy number variants are prevalent in agenesis of the corpus callosum but not in cerebellar hypoplasia or polymicrogyria.
Duplication
Large-scale discovery of novel genetic causes of developmental disorders.
Deletion
Performance of case-control rare copy number variation annotation in classification of autism.
Duplication
Cases
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
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
179730
0
2
2
fitzgerald_14_ASD/DD/ID_discovery_cases
Children recruited through all 24 regional genetics services of the UK National Health Service and Republic of Ireland as part of the Deciphering Developmental Disorders Study
1133
Cases affected by severe, undiagnosed developmental disorders; most common phenotypes include developmental delay, intellectual disability, specific learning disability, autism, seizures, microcephaly, and dysmorphic features.
Median age, 5.5 years
N/A
1561944
1
0
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
183138
0
1
1
gai_11_ASD_replication_cases
Replication case samples derived from AGRE sets 1-3
593
Idiopathic autism; cases designated as 'spectrum' and 'not quite autism' excluded, as were cases with known genetic syndromes or other non-idiopathic causes
202615
0
2
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
1541785
0
8
8
krumm_13_ASD_discovery_cases
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
Diagnosis of ASD. Social Responsiveness Scale (SRS) used as a quantitative measure of social deficits
N/A
81.265% Male
156270
0
2
2
krumm_15_ASD_discovery_cases
Probands from the Simons Simplex Collection
2377
Diagnosis of ASD
N/A
N/A
156270
0
3
3
o'roak_12_ASD_discovery_cases
Autistic probands from the Simons Simplex Collection (SSC), from an initial cohort of 189 autism families
122
ASD/autism
NA
NA
260882
0
1
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
127360
0
1
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
184418
0
1
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
178295
0
1
1
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
0
0
0
0
krumm_15_ASD_discovery_controls
Unaffected siblings from quad families from the Simons Simplex Collection
1786
Control
N/A
N/A
156270
0
1
1
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)
156274
0
1
1
sanders_11_ASD_discovery_controls
Matched siblings of autistic probands from the Simons Simplex Collection (SSC).
872
Controls
Mean, 10.0 yrs.
179046
0
2
2
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
engchuan_15_ASD_discovery_cases
Caucasian
Solid phase hybridization
Illumina 1M
None
fitzgerald_14_ASD/DD/ID_discovery_cases
UK and Ireland
aCGH, WES
Agilent 2x1M, Agilent Exome+
Cnsolidate, CoNVex
None
gai_11_ASD_discovery_cases
European
Solid phase hybridization
Illumina Infinium II HumanHap550 BeadChip
BeadStudio 3.0
qPCR
gai_11_ASD_replication_cases
European
Solid phase hybridization
Illumina Infinium II HumanHap550 BeadChip
BeadStudio 3.0
qPCR
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_13_ASD_discovery_cases
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
krumm_15_ASD_discovery_cases
N/A
WES
CoNIFER, XHMM
Solid phase hybridization (Illumina 1M, 1 M Duo, or Omni 2.5)
o'roak_12_ASD_discovery_cases
NA
WES
NimbleGen EZ Exome V2.0, Illumina GAIIx or HiSeq2000
HMM
mrsFAST aligner
aCGH, Sanger sequencing
sajan_13_ACC/CBLH/PMG_discovery_cases
81.31% Caucasian
Solid phase hybridization
Illumina InfiniumII HumanHap610
PennCNV
None (not tested or failure to confirm by 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
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
krumm_15_ASD_discovery_controls
N/A
WES
CoNIFER, XHMM
Solid phase hybridization (Illumina 1M, 1 M Duo, or Omni 2.5)
poultney_13_ASD_discovery_controls
European
WES
Agilent SureSelect Human All Exon v.2
XHMM
None
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
engchuan_15_ASD_discovery_cases-case13177_1943
N/A
N/A
ASD
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
34349261
34528992
179732
GRCh38
Duplication
No
engchuan_15_ASD_discovery_cases-case16037_1571015001
N/A
N/A
ASD
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
34353927
34528992
175066
GRCh38
Duplication
No
fitzgerald_14_ASD/DD/ID_discovery_cases-DECIPHER260592
N/A
M
Autism
Bifid uvula; Submucous cleft hard palate; Pectus excavatum; Autism with high cognitive abilities
33931763
35493713
1561951
GRCh38
Deletion
No
gai_11_ASD_discovery_cases-AU1510301
Autism
34643430
34826567
183138
Unknown
Duplication
Yes
gai_11_ASD_replication_cases-AU067404
Autism
34623953
34826567
202615
Unknown
Duplication
Yes
gai_11_ASD_replication_cases-AU074704
Autism
34639061
34826567
187507
Unknown
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00000111
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
34362355
34507461
145107
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001034
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
34362355
34507461
145107
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001626
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
34368690
34529083
160394
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001816
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
34368690
34529083
160394
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001823
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
34368690
34529083
160394
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00004061
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
34368619
34516695
148077
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00005042
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
34368619
34528119
159501
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00005157
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
33920512
35462303
1541792
GRCh38
Duplication
Yes
krumm_13_ASD_discovery_cases-case12507.p1
N/A
M
ASD
ASD proband from SSC quad family 12507. SRS score of 89.
Full-scale IQ (FSIQ) score of 80.
34370478
34526749
156272
GRCh38
Duplication
No (not tested)
krumm_13_ASD_discovery_cases-case13327.p1
N/A
M
ASD
ASD proband from SSC quad family 13327. SRS score of 90.
Full-scale IQ (FSIQ) score of 103.
34370478
34526749
156272
GRCh38
Duplication
No (not tested)
krumm_15_ASD_discovery_cases-case12507.p1
N/A
Male
ASD
Proband from the Simons Simplex Collection (SSC). Family type: Quad
34370478
34526749
156272
GRCh38
Duplication
Yes
krumm_15_ASD_discovery_cases-case13327.p1
N/A
Male
ASD
Proband from the Simons Simplex Collection (SSC). Family type: Quad
34370478
34526749
156272
GRCh38
Duplication
Yes
krumm_15_ASD_discovery_cases-case13844.p1
N/A
Male
ASD
Proband from the Simons Simplex Collection (SSC). Family type: Trio
34370478
34526749
156272
GRCh38
Duplication
Yes
o'roak_12_ASD_discovery_cases-case13844.p1
99 mos.
M
Autism
Case also identified to have de novo CHD8 truncating and de novo CUBN truncating mutations, and de novo TRAPPC8 synonymous mutation. Clinical range deficits in social responsiveness (120). Possible loss of language skills during development and elevated social withdrawal behaviors with no comorbid diagnoses. Food allergies (gluten and casein). Gastrointestinal constipation diagnosis with bloating and abdominal pain. Roseola diagnosed at 2.5 years and Epstein bar virus contracted at 8 years. Respiratory problems diagnosed at 11 months and kidney problems diagnosed at 9 months. No diagnosis of cardiac or metabolic syndromes noted. No report of congenital anomalies. NICU admission shortly after birth with oxygen treatment. Meconium aspiration at birth. Currently on GFCF diet. Took asthma medication in the past but not currently. Growth parameters: large head (z = 2.62), normal BMI. Family history: father with normative range of social responsiveness, but elevated score for rigidity on broader autism phenotype, some signs of alcoholism; mother currently taking thyroid medication and antidepressant (not taken during pregnancy); older sibling with behavioral elevations for somatic problems and complaints, cognitive decline following Ebstein-Barr virus reported by parents; maternal cousin with Down syndrome; family history for migraines among several members.
Extremely low VIQ (20), NVIQ (34), and adaptive (59) scores.
34354129
34615011
260883
GRCh38
Duplication
Yes
sajan_13_ACC/CBLH/PMG_discovery_cases-caseLR05-369
N/A
N/A
CBLH
Diagnosis of cerebellar hypoplasia (CBLH).
34401633
34528992
127360
GRCh38
Duplication
No
sanders_11_ASD_discovery_cases-13327.p1
12.6
M
Aspergers
NA
Full-scale IQ, 103; non-verbal IQ, 95; verbal IQ, 118
34350696
34535115
184420
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-controlHABC_902446_902446
N/A
N/A
Control
No previous psychiatric history
34350696
34528992
178297
GRCh38
Duplication
No
krumm_15_ASD_discovery_controls-control14491.s1
N/A
Male
Control
Unaffected sibling from the Simons Simplex Collection (SSC)
34370478
34526749
156272
GRCh38
Duplication
Yes
poultney_13_ASD_discovery_controls-control04C29561A
N/A
F
Control
NIMH Control (NIMH ID 61787)
34370477
34526751
156275
GRCh38
Duplication
No
sanders_11_ASD_discovery_controls-11321.s1
15.2
F
Control (matched sibling)
NA
NA
34353352
34532399
179048
GRCh38
Duplication
No
sanders_11_ASD_discovery_controls-12507.s1
26.1
F
Control (matched sibling)
NA
NA
34352440
34528992
176553
GRCh38
Duplication
No
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
engchuan_15_ASD_discovery_cases-case13177_1943
Unknown
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
engchuan_15_ASD_discovery_cases-case16037_1571015001
Unknown
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
fitzgerald_14_ASD/DD/ID_discovery_cases-DECIPHER260592
De novo
Simplex
Segregated
RPS5P2,KCNE2,FAM243A,RPL34P3,LINC00310,SMIM11A,SMIM34A,CLIC6,LINC01426,LINC00649,MRPS6,SLC5A3,KCNE1,LINC00160,RCAN1,RUNX1
gai_11_ASD_discovery_cases-AU1510301
qPCR
Inherited
KCNE2, FAM165B, KCNE1, RCAN1
gai_11_ASD_replication_cases-AU067404
qPCR
Inherited
KCNE2, FAM165B, KCNE1, RCAN1
gai_11_ASD_replication_cases-AU074704
qPCR
Inherited
KCNE2, FAM165B, KCNE1, RCAN1
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00000111
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Paternal
Unknown
Unknown
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001034
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Maternal
Unknown
Unknown
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001626
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001816
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Maternal
Unknown
Unknown
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001823
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00004061
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Maternal
Unknown
Unknown
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00005042
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00005157
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
RPS5P2,KCNE2,FAM243A,LINC00310,SMIM11A,SMIM34A,CLIC6,LINC01426,LINC00649,MRPS6,SLC5A3,KCNE1,LINC00160,RCAN1,RUNX1
krumm_13_ASD_discovery_cases-case12507.p1
Maternal
Simplex
Not segregated
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
krumm_13_ASD_discovery_cases-case13327.p1
Paternal
Simplex
Segregated
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
krumm_15_ASD_discovery_cases-case12507.p1
Illumina 1MDuo
Maternal
Simplex
Segregated
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
krumm_15_ASD_discovery_cases-case13327.p1
Illumina 1MDuo
Paternal
Simplex
Segregated
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
krumm_15_ASD_discovery_cases-case13844.p1
Omni2.5-4v1
Maternal
Simplex
Segregated
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
o'roak_12_ASD_discovery_cases-case13844.p1
aCGH, Sanger sequencing
Maternal
Simplex (quad)
Unknown
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
sajan_13_ACC/CBLH/PMG_discovery_cases-caseLR05-369
Not tested by qPCR
Unknown
Unknown
Unknown
SMIM11A,SMIM34A,KCNE1,RCAN1
sanders_11_ASD_discovery_cases-13327.p1
Paternal
Simplex (quad-proband matched)
Segregated
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
Controls
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
engchuan_15_ASD_discovery_controls-controlHABC_902446_902446
Unknown
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
krumm_15_ASD_discovery_controls-control14491.s1
Omni2.5-4v1
Maternal
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
poultney_13_ASD_discovery_controls-control04C29561A
Unknown
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
sanders_11_ASD_discovery_controls-11321.s1
Maternal
Simplex (quad)
NA
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
sanders_11_ASD_discovery_controls-12507.s1
Maternal
Simplex (quad)
NA
KCNE2,FAM243A,SMIM11A,SMIM34A,KCNE1,RCAN1
No Animal Model Data Available