12q21.2-q21.31CNV Type: Duplication
Largest CNV size: 98969 bp
Statistics Box:
Number of Reports: 6
Number of Reports: 6
Summary Information
Summary statement in development
Additional Locus Information
References
Major Reports
Title
Author, Year
Report Class
CNV Type
Functional impact of global rare copy number variation in autism spectrum disorders.
Duplication
An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabili...
Deletion-Duplication
Chromosomal microarray testing in adults with intellectual disability presenting with comorbid psychiatric disorders.
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.
Duplication
A discovery resource of rare copy number variations in individuals with autism spectrum disorder.
Duplication
Cases
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
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
7806063
1
1
2
maini_18_ASD/DD/ID_discovery_cases
Patients evaluated at the Clinical Genetics Unit of Arcispedale Santa Maria Nuova, AUSL-IRCCS of Reggio Emilia that were investigated through aCGH between 2005 and 2016
293
Cases presented with one or more neurodevelopmental disorders (NDD), multiple congenital anomalies (MCA), and/or dysmorphic features. Most frequent neurodevelopmental diagnoses include language delay (78.5%), intellectual disability (66.4%), motor delay (50.7%), and ASD (13.9%); dysmorphic features were also frequently observed (52.7%)
Mean age, 7 yrs. (range, 1 mo.-29 yrs.)
57.5% Male
7463000
0
6
6
pinto_10_ASD_discovery_cases
Autism Genome Project (AGP) consortium patient cohort from families with at least two ASD individuals
996
ASD (ADI-R and ADOS): strict, broad, or spectrum ASD
98969
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
100986
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
41406
0
1
1
wolfe_16_ID_discovery_cases
Patients recruited via the Mental Health Research Network (MHRN) at 32 National Health Service (NHS) trusts and 1 non-NHS provider across England between August 2012 and March 2014.
202
All cases presented with intellectual disability. Clinical data including medical and psychiatric history (ICD-10 diagnoses) was collected from an informant and/or medical records; detailed psychiatric and behavioral phenotyping undertaken using the Mini Psychiatric Assessment Schedule for Adults with Developmental Disabilities (Mini PAS-ADD) and Behaviour Problems Inventory-Short Form (BPI-S).
Mean age, 37 yrs. (range, 18-78 yrs.)
63% Male
5001177
1
0
1
Controls
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
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
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)
100986
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.
0
0
0
0
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
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
maini_18_ASD/DD/ID_discovery_cases
Italian
aCGH, array SNP
Multiple platforms, including Agilent and Affymetrix arrays (8x60K oligochips since 2012)
None
pinto_10_ASD_discovery_cases
European
Solid phase hybridization
Illumina Infinium 1M SNP microarray
QuantiSNP, iPattern
qPCR, long-range PCR (LR-PCR), MLPA, FISH, aCGH (Agilent 1M), array SNP (Affymetrix 500K)
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
wolfe_16_ID_discovery_cases
74% White British
aCGH
Nimblegen 135K
qPCR, FISH, QF-PCR
Controls
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
kaminsky_11_DD/ID/ASD_discovery_controls
NA
aCGH
Agilent 44K, Agilent 105K
Feature Extraction, DNA Analytics
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
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00000867
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
75683698
80195649
4511952
GRCh38
Deletion
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001981
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
77564757
85370822
7806066
GRCh38
Duplication
Yes
maini_18_ASD/DD/ID_discovery_cases-case104
12 yrs.
F
Language delay, language disorder, and learning disorder
Birth history: born at 40 weeks gestation, no reported pregnancy anomalies. Developmental milestones: language delay. Language and communication evaluation: language disorder. Musculoskeletal evaluation: brachydactyly, clinodactyly F5, short and large feet with large toes. Behavioral/psychiatric evaluation: behavioral anomalies. Epilepsy/abnormal EEG: no reported epilepsy or EEG abnormalities. Additional medical history: congenital heart defects, ocular anomalies. Dysmorphic features: arched and tight eyebrows, blepharophimosis, ptosis, epicanthus inversus, telecanthus, bulbous nose, posteriorly rotated ears with overfolded helices. Growth parameters: normal head circumference, short stature. Family history: negative for consanguineity, positive for familiarity, family history positive for NDDs.
Learning disorder (no intellectual disability)
78163604
85640255
7476652
GRCh38
Tetrasomy
No
maini_18_ASD/DD/ID_discovery_cases-case192
2 yrs.
M
Dysmorphic features and kidney malformations
Birth history: born at 40 weeks gestation, no reported pregnancy anomalies. Developmental milestones: no motor or language delay. Language and communication evaluation: no language disorder or absent speech. Behavioral/psychiatric evaluation: no reported behavioral or psychiatric abnormalities. Epilepsy/abnormal EEG: no reported epilepsy or EEG abnormalities. Additional medical history: kidney malformations. Dysmorphic features: unilateral ptosis, epicanthus, tented upper lip. Growth parameters: normal head circumference, normal growth. Family history: negative for consanguineity, positive for familiarity, family history positive for NDDs.
Normal (no intellectual disability or learning disorder)
78163604
85640255
7476652
GRCh38
Tetrasomy
No
maini_18_ASD/DD/ID_discovery_cases-case193
9 yrs.
M
Language delay and language disorder
Birth history: born at 38 weeks gestation, no reported pregnancy anomalies. Developmental milestones: language delay. Language and communication evaluation: language disorder. Musculoskeletal evaluation: 5th finger clinodactyly, bulbous hallux of the toes. Behavioral/psychiatric evaluation: behavioral anomalies. Epilepsy/abnormal EEG: no reported epilepsy or EEG abnormalities. Dysmorphic features: bilateral ptosis, epicanthus, hypertelorism, posteriorly rotated ears with thick helices. Growth parameters: normal head circumference, short stature. Family history: negative for consanguineity, positive for familiarity, family history positive for NDDs.
Normal (no intellectual disability or learning disorder)
78163604
85640255
7476652
GRCh38
Tetrasomy
No
pinto_10_ASD_discovery_cases-case5523_3
NA
F
ASD
NA
NA
79722153
79821121
98969
GRCh38
Duplication
Yes
prasad_12_ASD_discovery_cases-case122712L
NA
F
ASD
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS. CNV identified by previous SNP microarray study
78640553
78741538
100986
Unknown
Duplication
No
sanders_11_ASD_discovery_cases-13038.p1
8.8
M
Autism
NA
Full-scale IQ, 96; non-verbal IQ, 94; verbal IQ, 100
79772314
79813720
41407
GRCh38
Duplication
No
wolfe_16_ID_discovery_cases-DECIPHER327126
31 yrs.
M
Intellectual disability and schizophrenia
Psychiatric history: schizophrenia, alcohol abuse, on forensic in-patient section. Mini PAS-ADD evaluation: hypomania, psychosis. BPI-S evaluation: any self-injurious, aggressive/destructive, or stereotyped behaviors occur less than weekly. Medical history: none recorded. Dysmorphic features: hypertelorism, depressed nasal bridge, wide nasal bridge, low set ears, microtia. Growth parameters: height 169 cm, head circumference 64 cm. Ethnicity: black (African).
Mild intellectual disability
79140868
84142045
5001178
GRCh38
Deletion
Yes
Controls
No Control Data Available
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00000867
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Maternal
Unknown
Unknown
RPL10P13,RN7SL734P,PHLDA1,RNU6-1271P,RN7SKP172,BBS10,RPL7AP9,YWHAQP7,RPL7P43,LINC02464,MIR1252,NOP56P3,RNA5SP363,SNRPGP20,RPL7P38,RNU7-106P,NAP1L1,CSRP2,E2F7,LINC02424,PAWR,PPP1R12A-AS1,ZDHHC17,SYT1,PPP1R12A,OTOGL,OSBPL8,NAV3
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001981
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
MIR1252,NOP56P3,RNA5SP363,SNRPGP20,RPL7P38,RNU7-106P,RN7SKP261,AKIRIN1P1,MYF5,LINC01490,MIR617,MIR618,MIR4699,RNU6-977P,RPL6P25,LINC02424,PAWR,PPP1R12A-AS1,MYF6,PPFIA2-AS1,LINC02426,SLC6A15,TSPAN19,ALX1,SYT1,PPP1R12A,OTOGL,PTPRQ,LIN7A,ACSS3,PPFIA2,CCDC59,METTL25,LRRIQ1,NAV3,TMTC2
maini_18_ASD/DD/ID_discovery_cases-case104
Maternal
Not simplex
Unknown
MIR1252,NOP56P3,RNA5SP363,SNRPGP20,RPL7P38,RNU7-106P,RN7SKP261,AKIRIN1P1,MYF5,LINC01490,MIR617,MIR618,MIR4699,RNU6-977P,RPL6P25,LINC02424,PAWR,PPP1R12A-AS1,MYF6,PPFIA2-AS1,LINC02426,SLC6A15,TSPAN19,ALX1,SYT1,PPP1R12A,OTOGL,PTPRQ,LIN7A,ACSS3,PPFIA2,CCDC59,METTL25,LRRIQ1,NAV3,TMTC2
maini_18_ASD/DD/ID_discovery_cases-case192
Maternal
Not simplex
Unknown
MIR1252,NOP56P3,RNA5SP363,SNRPGP20,RPL7P38,RNU7-106P,RN7SKP261,AKIRIN1P1,MYF5,LINC01490,MIR617,MIR618,MIR4699,RNU6-977P,RPL6P25,LINC02424,PAWR,PPP1R12A-AS1,MYF6,PPFIA2-AS1,LINC02426,SLC6A15,TSPAN19,ALX1,SYT1,PPP1R12A,OTOGL,PTPRQ,LIN7A,ACSS3,PPFIA2,CCDC59,METTL25,LRRIQ1,NAV3,TMTC2
maini_18_ASD/DD/ID_discovery_cases-case193
Maternal
Not simplex
Unknown
MIR1252,NOP56P3,RNA5SP363,SNRPGP20,RPL7P38,RNU7-106P,RN7SKP261,AKIRIN1P1,MYF5,LINC01490,MIR617,MIR618,MIR4699,RNU6-977P,RPL6P25,LINC02424,PAWR,PPP1R12A-AS1,MYF6,PPFIA2-AS1,LINC02426,SLC6A15,TSPAN19,ALX1,SYT1,PPP1R12A,OTOGL,PTPRQ,LIN7A,ACSS3,PPFIA2,CCDC59,METTL25,LRRIQ1,NAV3,TMTC2
pinto_10_ASD_discovery_cases-case5523_3
Agilent1M
maternal
NA
NA
PPP1R12A
prasad_12_ASD_discovery_cases-case122712L
Unknown
Unknown
Unknown
PPP1R12A
sanders_11_ASD_discovery_cases-13038.p1
Maternal
Simplex (quad-proband matched)
Segregated
PPP1R12A
wolfe_16_ID_discovery_cases-DECIPHER327126
qPCR, FISH, or QF-PCR
Unknown
Unknown
Unknown
MIR1252,NOP56P3,RNA5SP363,SNRPGP20,RPL7P38,RNU7-106P,RN7SKP261,AKIRIN1P1,MYF5,LINC01490,MIR617,MIR618,MIR4699,RNU6-977P,RPL6P25,PAWR,PPP1R12A-AS1,MYF6,PPFIA2-AS1,LINC02426,SYT1,PPP1R12A,OTOGL,PTPRQ,LIN7A,ACSS3,PPFIA2,CCDC59,METTL25,TMTC2
Controls
No Control Data Available
No Animal Model Data Available