21q21.1-q21.2CNV Type: Deletion
Largest CNV size: 98808 bp
Statistics Box:
Number of Reports: 7
Number of Reports: 7
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.
Deletion
An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabili...
Deletion
21q21 deletion involving NCAM2: report of 3 cases with neurodevelopmental disorders.
Deletion
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
Duplication
Minor Reports
Title
Author, Year
Report Class
CNV Type
A discovery resource of rare copy number variations in individuals with autism spectrum disorder.
Deletion
Performance of case-control rare copy number variation annotation in classification of autism.
Deletion
Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder.
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
76941
1
0
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
5071213
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
98808
1
0
1
petit_14_DD_discovery_cases
Three cases present in the DECIPHER database affected with developmental delay and carrying 21q21 deletions involving the NCAM2 gene
3
All three cases present with global developmental delay. Cases 1 & 3 also present with impaired social interactions; cases 1 & 2 present with behavioral problems.
Range, 5 yrs. 3 mos.-8.5 yrs.
66.67% Male
8500000
3
0
3
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
74989
1
0
1
yin_16_ASD_discovery_cases
Discovery cohort of ASD cases recruited from the Department of Psychiatry of National Taiwan University Hospital (NTUH), Chang Gung Memorial Hospital (CGMH), Taoyuan, and Taoyuan Mental Hospital (TMH), Taiwan.
335
Cases diagnosed with autistic disorder according to DSM-IV and confirmed by using the Chinese version of ADI-R. Cases' autistic behaviors assessed by Social Responsiveness Scale (SRS), and cognitive functions assessed by the Weschler Intelligence Scale for Children-Third Edition (WISC-III) and the Wisconsin Card Sorting Test (WCST).
Mean, 9.39 4.04 yrs.
89.3% Male
821735
0
1
1
yuen_17_ASD_discovery_cases
ASD genomes (1745 ASD probands, 879 ASD-affected siblings, 1 ASD-affected father, and 1 ASD-affected grandfather) from AGRE (n=730), the AGRE; Autism Treatment Network cohort (n=192) ,the ASD: Genomes to Outcomes Study cohort (n=1421), the Baby Siblings Research Consortium (n=43), the Baby Siblings Research Consortium; The Autism Simplex Collection cohort (n=6), the Infant Sibling Study (n=62), th
2626
ASD diagnosis of research quality when meeting criteria on one (n=437) or both (n=1361) of the diagnostic measures ADI-R and ADOS; clinical diagnosis of ASD (n=819) when given by expert clinician according to DSM-IV or DSM-5
N/A
78.71% Male
6262999
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
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
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)
74989
0
0
0
yin_16_ASD_discovery_controls
Individuals from the Han Chinese Cell and Genome Bank (HCCGB) in Taiwan
1093
Controls
Mean, 68.07 10.12 yrs.
48.0% Male
821735
0
0
0
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
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
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
petit_14_DD_discovery_cases
2 cases of French origin, 1 case Caucasian
aCGH
Agilent 60K, BlueGnome ISCA 60K v2.0
Cytogenetics v2.7.22, BlueFuse Multi
qPCR, FISH, G-banded karyotyping
prasad_12_ASD_discovery_cases
Canada
aCGH
Agilent 1M
ADM-2, DNAcopy (R Bioconductor)
DNA Analytics v4.0.85 (Agilent), DNAcopy
None
yin_16_ASD_discovery_cases
Han Chinese
Array SNP
Affymetrix 6.0
Affymetrix Genotyping Console v.4.1
None
yuen_17_ASD_discovery_cases
N/A
WGS
Complete Genomics, Illumina HiSeq 2000, HiSeq X
aCGH (Agilent 1M), array SNP (Affymetrix 6.0, Affymetrix CytoScan HD), solid phase hybridization (Illumina 1M, Illumina OMNI 2.5M)
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
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
yin_16_ASD_discovery_controls
Han Chinese
Array SNP
Affymetrix 6.0
Affymetrix Genotyping Console v.4.1
None
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-case5078_4
N/A
N/A
ASD
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
22548427
22625368
76942
GRCh38
Deletion
No
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002618
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
20327525
25398738
5071214
GRCh38
Deletion
Yes
marshall_08_ASD_discovery_cases-MM0126-003
NA
M
ASD
NA
NA
22545380
22644187
98808
GRCh38
Deletion
Yes
petit_14_DD_discovery_cases-case1
7 yrs. 7 mos.
M
Developmental delay
Case present in DECIPHER database (#276325). Birth/neonatal history: born at term after uneventful pregnancy; birth weight of 4630 g (+2.5 SD), height of 53.5 cm (+3 SD), and OFC of 37 cm (+1 SD); chronic purpura related to capillary fragility during first months of life. Developmental milestones: global developmental delay; sat at 13 months, walked at 2 years, first words' association at 4 years. Language and communication evaluation: able to write few letters, reading not acquired. Motor and musculoskeletal evaluation: joint laxity. Behavioral/psychiatric evaluation: impaired social interactions; behavioral issues including attention deficit, impairment of eye contact, distress at changes or frustration, and aggression. Dysmorphic features: large ears, epicanthal folds, brachycephaly, sandal gap. Family history: first child of non-consanguineous parents of French origin; father is healthy and has no particular family history; mother had speech delay in infancy and school difficulties; maternal grandparents were poorly socially adapted and cannot read or write.
Verbal IQ of 58 and performance IQ of 87 at age of 6 years.
21062316
24943120
3880805
GRCh38
Deletion
Yes
petit_14_DD_discovery_cases-case2
8.5 yrs.
M
Developmental delay
Case present in DECIPHER database (#254181). Birth/neonatal history: born at term after uneventful pregnancy, except for maternal treatment by sodium valproate (1 g/d); birth weight of 2540 g (-2 SD), height of 46 cm (-2.5 SD), and OFC of 35 cm (0 SD); surgery for bilateral cryptorchidism at age of 4 months. Developmental milestones: global developmental delay; walking acquired at 23 months; speech delay. Language and communication evaluation: beginning to read. Behavioral/psychiatric evaluation: behavioral issues with hyperactivity. Dysmorphic features: epicanthal folds, long and flat philtrum, high palate, low-set ears. Growth parameters: weight of 26.9 kg (0 SD), height of 131 cm (+0.5 SD), and OFC of 54 cm (+1 SD). Family history: child of non-consanguineous parents of French origin; mother treated for epilepsy; father has no neurological or psychiatric problems but has mildly impaired social ineractions (his brother and parents have no neurological issues).
Attends school in specialized class
15619936
23525918
7905983
GRCh38
Deletion
Yes
petit_14_DD_discovery_cases-case3
5 yrs. 3 mos.
F
Developmental delay
Case present in DECIPHER database (#274603). Birth/neonatal history: very little information on pregnancy and birth parameters. Developmental milestones: global developmental delay; walking acquired at 2.5 years, first words at 3 years, toilet-trained at 3.5 years for day-time but night-time toilet training not yet achieved. Language and communication evaluation: able to make sentences and write her first name. Motor and musculoskeletal evaluation: hypotonia, joint laxity (particularly of knees). Behavioral/psychiatric evaluation: impaired social interactions. Dysmorphic features: almond-shaped eyes. Growth parameters: weight of 24.7 kg (+3 SD), height of 113 cm (+1.5 SD), and OFC of 51 cm (+1 SD). Family history: adopted; biological father had learning difficulties (details not known); father shows somatic mosaicism for 21q21.1-q21.2 deletion.
Follows an individual educational plan and is taught with children a year younger.
16079383
24575840
8496458
GRCh38
Deletion
Yes
prasad_12_ASD_discovery_cases-case47378
NA
M
ASD
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS. CNV identified by previous SNP microarray study
22838399
22913387
74989
Unknown
Deletion
No
yin_16_ASD_discovery_cases-case607
N/A
N/A
ASD
Cases diagnosed with autistic disorder according to DSM-IV and confirmed by using the Chinese version of ADI-R.
22544275
23366006
821732
GRCh38
Duplication
No
yuen_17_ASD_discovery_cases-case1-0204-004
N/A
N/A
ASD
Case cohort: ASD: Genomes to Outcome Study. Clinical description: N/A
18327684
24590686
6263003
GRCh38
Duplication
Yes
Controls
No Control Data Available
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
engchuan_15_ASD_discovery_cases-case5078_4
Unknown
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002618
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Maternal
Unknown
Unknown
RNU6-772P,RN7SKP147,FDPSP6,KRT18P2,RPS3AP1,PPIAP1,RNU4-45P,MAPK6P2,MIR6130,ZNF299P,RNU2-55P,EEF1A1P1,TUBAP,RN7SKP236,RNA5SP489,RPL13AP7,LINC00320,LINC00317,LINC00308,MSANTD2P1,D21S2088E,LINC01689,NCAM2,LINC01425,LINC01684,LINC01692,LINC00158,LINC01687
marshall_08_ASD_discovery_cases-MM0126-003
qPCR, qmPCR
Unknown
NA
NA
petit_14_DD_discovery_cases-case1
qPCR
Maternal
Maternal
Multi-generational
Likely segregated
RNU4-45P,MAPK6P2,MIR6130,ZNF299P,RNU2-55P,EEF1A1P1,TUBAP,LINC00317,LINC00308,MSANTD2P1,D21S2088E,LINC01689,NCAM2,LINC01425,LINC01684,LINC01692,LINC01687
petit_14_DD_discovery_cases-case2
FISH
Maternal and/or paternal
Unknown
Possibly multi-generational
Unknown
RNU6-426P,VDAC2P1,RPS26P5,SNORD74B,MIR99A,MIRLET7C,MIR125B2,RNU1-98P,NEK4P1,RNU6-113P,RPL39P40,RN7SL163P,BTF3L4P1,RPL37P3,MIR548X,SLC6A6P1,RNU1-139P,RPL37P4,C1QBPP1,LINC01683,LINC02573,RNU6-772P,RN7SKP147,FDPSP6,KRT18P2,RPS3AP1,PPIAP1,RNU4-45P,MAPK6P2,MIR6130,ZNF299P,RNU2-55P,EEF1A1P1,TUBAP,RAD23BP3,RBPMSLP,LINC01549,BTG3,BTG3-AS1,C21orf91-OT1,C21orf91,CHODL-AS1,PPIAP22,LINC00320,LINC00317,LINC00308,MSANTD2P1,D21S2088E,USP25,MIR99AHG,CXADR,CHODL,TMPRSS15,MIR548XHG,NCAM2,LINC01425,LINC01687
petit_14_DD_discovery_cases-case3
G-banded karyotyping
Paternal
Paternal
Multi-generational
Likely segregated
VDAC2P1,RPS26P5,SNORD74B,MIR99A,MIRLET7C,MIR125B2,RNU1-98P,NEK4P1,RNU6-113P,RPL39P40,RN7SL163P,BTF3L4P1,RPL37P3,MIR548X,SLC6A6P1,RNU1-139P,RPL37P4,C1QBPP1,LINC01683,LINC02573,RNU6-772P,RN7SKP147,FDPSP6,KRT18P2,RPS3AP1,PPIAP1,RNU4-45P,MAPK6P2,MIR6130,ZNF299P,RNU2-55P,EEF1A1P1,TUBAP,LINC01549,BTG3,BTG3-AS1,C21orf91-OT1,C21orf91,CHODL-AS1,PPIAP22,LINC00320,LINC00317,LINC00308,MSANTD2P1,D21S2088E,LINC01689,MIR99AHG,CXADR,CHODL,TMPRSS15,MIR548XHG,NCAM2,LINC01425,LINC01684,LINC01687
prasad_12_ASD_discovery_cases-case47378
Unknown
Unknown
Unknown
0 genes
yin_16_ASD_discovery_cases-case607
Unknown
Unknown
Unknown
MIR6130,ZNF299P,RNU2-55P,MSANTD2P1,D21S2088E
yuen_17_ASD_discovery_cases-case1-0204-004
Affymetrix 6.0
Unknown
Multiplex
Unknown
MIR548X,SLC6A6P1,RNU1-139P,RPL37P4,C1QBPP1,LINC01683,LINC02573,RNU6-772P,RN7SKP147,FDPSP6,KRT18P2,RPS3AP1,PPIAP1,RNU4-45P,MAPK6P2,MIR6130,ZNF299P,RNU2-55P,EEF1A1P1,TUBAP,PPIAP22,LINC00320,LINC00317,LINC00308,MSANTD2P1,D21S2088E,LINC01689,TMPRSS15,MIR548XHG,NCAM2,LINC01425,LINC01684,LINC01687
Controls
No Control Data Available
No Animal Model Data Available