12p13.1CNV Type: Deletion
Largest CNV size: 11907 bp
Statistics Box:
Number of Reports: 11
Number of Reports: 11
Summary Information
Summary statement in development
Additional Locus Information
References
Major Reports
Title
Author, Year
Report Class
CNV Type
Evaluation of copy number variations reveals novel candidate genes in autism spectrum disorder-associated pathways.
Deletion
Deficiency of the cyclin-dependent kinase inhibitor, CDKN1B, results in overgrowth and neurodevelopmental delay.
Deletion
Interstitial 12p13.1 deletion involving GRIN2B in three patients with intellectual disability.
Deletion
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.
Deletion
Chromosomal microarray testing in adults with intellectual disability presenting with comorbid psychiatric disorders.
Duplication
Minor Reports
Title
Author, Year
Report Class
CNV Type
Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.
Deletion
A discovery resource of rare copy number variations in individuals with autism spectrum disorder.
Deletion-Duplication
Identification of small exonic CNV from whole-exome sequence data and application to autism spectrum disorder.
Duplication
Performance of case-control rare copy number variation annotation in classification of autism.
Deletion
Paternally inherited cis-regulatory structural variants are associated with autism.
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
105
1
0
1
dimassi_13_ID/DD_discovery_cases
Three patients presenting similar phenotypes with overlapping interstitial 12p13.1 microdeletions encompassing all or part of the GRIN2B gene
3
2 cases with intellectual disability, 1 case with developmental delay and autistic features; all 3 cases also presented with delayed language acquisition and mild facial dysmorphism.
Range, 3-24 yrs.
66.67% Male
587000
1
0
1
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
119069
2
0
2
grey_13_ASD/DD_discovery_cases
First child born to non-consanguineous Bengali parents
1
Autism (diagnostic tools N/A), severe developmental delay, and overgrowth
5 yrs. 6 mos.
Male
108776
1
0
1
griswold_12_ASD_discovery_cases
Unrelated ASD cases from the Collaborative Autism Project (CAP) ascertained through clinical groups at the University of Miami (HIHG), the University of South Carolina, and Vanderbilt University. 260 cases from multiplex families, 483 from simplex families, 62 from families with siblings having autistic-like traits without a confirmed ASD diagnosis, and 8 from families with monozygotic twins.
813
Daignosis of ASD/autism. Inclusion criteria: (1) age between 3-21 years, (2) presumptive clinical diagnosis of autism, (3) expert clinical determination of autism diagnosis using DSM-IV criteria supported by ADI-R in the majority of cases and all available clinical information, (4) minimal developmental level of 18 months as determined by VABS or VABS-II or IQ equivalent >35. Exclusion criteria: severe sensory problems, significant motor impairments, or previously identified metabolic, genetic, or progressive neurological disorder.
Range, 3-21 yrs.
NA
34987
1
0
1
leblond_12_ASD_replication_cases
Dataset featuring ASD patients from the Autism Genome Project carrying de novo SHANK2 deletions previously identified by Pinto et al. 2010. CNV validation information taken from Pinto report.
2
1 patient diagnosed with autism, 1 patient diagnosed with PDD-NOS.
NA
100% Male
11907
1
0
1
pinto_14_ASD_discovery_cases
ASD probands from simplex and multiplex families collected as part of stage 2 of the Autism Genome Project (AGP) after quality control (1,604 before QC)
1359
Cases classified according to ADOS and ADI-R
N/A
N/A
34988
1
0
1
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)
605260
0
4
4
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
17641
1
1
2
spataro_23_ASD/DD/ID_discovery_cases
Individuals from the Clinical Genetics Unit at Parc Tauli Hospital Universitari (Sabadell, Spain) between March 2019 and December 2021.
398
Cases had a clinical diagnosis of autism spectrum disorder (ASD) or global developmental delay/intellectual disability (DD/ID).
Average age, 14.5 +/- 11.2 yrs.
62.06% Male
1300
1
0
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
8262
0
1
1
Controls
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
brandler_18_ASD_discovery_controls
Unaffected individuals from the Relating Genes with Adolescent and Child Health (REACH) cohort (112 individuals from 311 families) and the Simons Simplex 1 (SSC1) cohort (518 controls from simplex quad families)
630
Control
N/A
N/A
105
1
0
1
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
griswold_12_ASD_discovery_controls
Children recruited as pediatric controls from HIHG (Miami, FL) and preterm birth study at Centennial Medical Center (Nashville, TN)
592
Control
Range, preterm-21 yrs.
NA
34987
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)
700556
0
1
1
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)
17641
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.
91580
0
1
1
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
None
dimassi_13_ID/DD_discovery_cases
France
aCGH
Agilent SurePrint G3 180K, Agilent 60K
qPCR
engchuan_15_ASD_discovery_cases
Caucasian
Solid phase hybridization
Illumina 1M
None
grey_13_ASD/DD_discovery_cases
Bengali
aCGH
Custom Agilent oligoarray
Sanger sequencing
griswold_12_ASD_discovery_cases
Range of self-reported ethnicities (specifics NA)
Solid phase hybridization
Illumina Human 1M-v1_C BeadChip, Illumina 1M-DuoV3 BeadChip
Penn CNV, QuantiSNP
BeadStudio
qPCR
leblond_12_ASD_replication_cases
1 Canadian, 1 French
Solid phase hybridization
Illumina 1M SNP array
QuantiSNP, PennCNV
None
pinto_14_ASD_discovery_cases
Predominantly European
Solid phase hybridization
Illumina 1M (v.1 and v.3)
qPCR, MLPA, long-range PCR
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
spataro_23_ASD/DD/ID_discovery_cases
Spain
Targeted gene sequencing
NNDTauliPanel/Illumina MiSeq
NA
XHMM, ExomeDepth
MLPA or aCGH
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
brandler_18_ASD_discovery_controls
N/A
WGS
Illumina HiSeq X10 or HiSeq 2500
ForestSV, Lumpy, Manta, Mobster, SV2
None
engchuan_15_ASD_discovery_controls
Caucasian
Solid phase hybridization
Illumina 1M
None
griswold_12_ASD_discovery_controls
Caucasian
Solid phase hybridization
Illumina Human 1M-v1_C BeadChip, Illumina 1M-DuoV3 BeadChip
Penn CNV, QuantiSNP
BeadStudio
poultney_13_ASD_discovery_controls
European
WES
Agilent SureSelect Human All Exon v.2
XHMM
None
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-caseSSC10622
N/A
M
ASD
Case from SSC_phase1 cohort
14424366
14424471
106
GRCh38
Deletion
No
dimassi_13_ID/DD_discovery_cases-case3
3 yrs.
M
Developmental delay and autistic features
Birth/neonatal history: born at full term after uneventful pregnancy; normal birth parameters (weight -1 SD, length -1 SD, OFC +1 SD); axial hypotonia and poor eye contact noted at age of 6 months. Developmental milestones: walking at 19 months, with physiotherapy support; delayed speech acquisition. Language and communication evaluation: delayed speech acquisition. Behavioral/psychiatric evaluation: autistic features/behavioral problems (aggression, stereotypies, pervasive developmental disorder). Dysmorphic features: high forehead with frontal upsweep, bilateral epicanthus. Brain imaging: normal brain MRI. Growth parameters: normal; height 97 cm, weight 15 kg, OFC 50.8 cm. Family history: second child of non-consanguineous parents.
Developmental delay
13910962
14498198
587237
GRCh38
Deletion
Yes
engchuan_15_ASD_discovery_cases-case4176_1
N/A
N/A
ASD
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
13709540
13744527
34988
GRCh38
Deletion
No
engchuan_15_ASD_discovery_cases-case6319_3
N/A
N/A
ASD
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
14049321
14168390
119070
GRCh38
Deletion
No
grey_13_ASD/DD_discovery_cases-case1
5 yrs. 6 mos.
M
ASD and developmental delay
Birth/neonatal history: born at full-term by C-section; birth weight 50th %ile, OFC 50th-75th %ile. Developmental milestones: significant developmental delay; language and manipulation skills at 33 months of age were at the 15 month level (age-appropriate motor skills). Language and communication evaluation: no speech at age of 5 years 6 months. Behavioral/psychiatric evaluation: challenging behavior due to severe autism (diagnostic tools N/A). Dysmorphic features: left-sided strabismus, maldescended testes. Growth parameters: overgrowth; height of 119.5 cm (91st-98th %ile), weight of 29.8 kg (>99.6th %ile), and OFC of 56.5 cm (>98th %ile). Family history: born to non-consanguineous Bengali parents of normal intellect; healthy younger sister. Other genetic features: proband carries a de novo variant in the CDKN1B promoter that results in decreased protein translation.
Developmental delay
12721944
12830719
108776
GRCh38
Deletion
Yes
griswold_12_ASD_discovery_cases-case7614
NA
NA
ASD/autism
NA
NA
13709540
13744527
34988
GRCh38
Deletion
Yes
leblond_12_ASD_replication_cases-Pintocase6319_3
NA
M
PDD-NOS
ADI-R domain scores: social, 14; communication, 8; behaviors, 2; age at first symptoms <36 months. Developmental milestones: delayed langauge (1st words at 24 months, 1st sentences at 48 months); no history of regression. Language and communication evaluation: delayed but functional language. Epilepsy/seizures: no history of epilepsy. Neurological examination: normal. Dysmorphic features: large and prominent ears, flat feet. Other comorbid medical conditions: hypermetropia.
Mild intellectual disability (ID). WISC-III IQ scores: full-scale IQ, 60; performance IQ, 60; verbal IQ, 67.
14049321
14168390
119070
GRCh38
Deletion
No
pinto_14_ASD_discovery_cases2-case4176_1
N/A
M
ASD
Clinical profile: N/A.
Cognitive profile: N/A.
13709540
13744527
34988
GRCh38
Deletion
Yes
poultney_13_ASD_discovery_cases-case03HI2580A
N/A
M
ASD
ASD case from AGRE (AGRE ID AU0924301; NDAR ID NDAR_INVCE056PE7)
14497652
14806682
309031
GRCh38
Duplication
No
poultney_13_ASD_discovery_cases-case99HI0694B
N/A
F
ASD
ASD case from AGRE (AGRE ID AU038203; NDAR ID NDAR_INVXX733FLA)
14506160
15111419
605260
GRCh38
Duplication
No
poultney_13_ASD_discovery_cases-case99HI1144B
N/A
M
ASD
ASD case from AGRE (AGRE ID AU020404; NDAR ID NDAR_INVPN168CVH)
14446986
14553414
106429
GRCh38
Duplication
No
poultney_13_ASD_discovery_cases-case99HI1144B
N/A
M
ASD
ASD case from AGRE (AGRE ID AU020404; NDAR ID NDAR_INVPN168CVH)
12822659
13076145
253487
GRCh38
Duplication
No
prasad_12_ASD_discovery_cases-case117372L
NA
F
ASD
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS. Novel CNV
12961498
12970139
8642
Unknown
Duplication
No
prasad_12_ASD_discovery_cases-case83680L
NA
F
ASD
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS. Novel CNV
12912518
12930158
17641
Unknown
Deletion
No
spataro_23_ASD/DD/ID_discovery_cases-case103
23.6 yrs.
M
Developmental delay and intellectual disability
Developmental milestones: global developmental delay. Behavioral/psychiatric evaluation: behavioral abnormality.
Moderate intellectual disability
13752966
13754265
1300
GRCh38
Deletion
Yes
wolfe_16_ID_discovery_cases-DECIPHER327120
68 yrs.
F
Intellectual disability
Psychiatric history: challenging behavior. Mini PAS-ADD evaluation: none met. BPI-S evaluation: at least weekly self-injurious behavior and aggressive/destructive behavior. Medical history: pes cavus (requiring callipers), gastric reflux. Dysmorphic features: no gross dysmorphology reported. Growth parameters: height 152 cm, head circumference 57 cm. Ethnicity: white (British).
Moderate intellectual disability
13601623
13609884
8262
GRCh38
Duplication
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
brandler_18_ASD_discovery_controls-controlSSC10629
N/A
M
Control
Control from SSC_phase1 cohort
14424366
14424471
106
GRCh38
Deletion
No
poultney_13_ASD_discovery_controls-control05C44621
N/A
M
Control
NIMH Control (NIMH ID 39000)
12975306
13675861
700556
GRCh38
Duplication
No
sanders_11_ASD_discovery_controls-11233.s1
4.7
M
Control (matched sibling)
NA
NA
14230578
14322158
91581
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-caseSSC10622
Not available
Maternal
ATF7IP
dimassi_13_ID/DD_discovery_cases-case3
qPCR
De novo
Simplex (based on family history provided in report)
Likely segregated
MRPS18CP4,RNU6-491P,GNAI2P1,RPL30P11,ATF7IP,GRIN2B
engchuan_15_ASD_discovery_cases-case4176_1
Unknown
GRIN2B
engchuan_15_ASD_discovery_cases-case6319_3
Unknown
grey_13_ASD/DD_discovery_cases-case1
Sanger sequencing
Maternal
Simplex
Segregated
CDKN1B,MIR613,STX8P1,APOLD1,DDX47
Four-fold decrease in CDKN1B mRNA expression
griswold_12_ASD_discovery_cases-case7614
qPCR
Maternal
Simplex
Segregated
GRIN2B
leblond_12_ASD_replication_cases-Pintocase6319_3
Maternal
pinto_14_ASD_discovery_cases2-case4176_1
qPCR (Griswold et al. 2011, PMID: 21360829)
Maternal
Simplex
(not tested)
GRIN2B
poultney_13_ASD_discovery_cases-case03HI2580A
Unknown
Unknown (likely multiplex/AGRE)
Unknown
RN7SKP134,HIST4H4,H2AFJ,PLBD1-AS1,WBP11,ATF7IP,PLBD1,C12orf60,SMCO3,GUCY2C
poultney_13_ASD_discovery_cases-case99HI0694B
Unknown
Unknown (likely multiplex/AGRE)
Unknown
RN7SKP134,HIST4H4,H2AFJ,MGP,LINC01489,PLBD1-AS1,WBP11,ART4,ERP27,PDE6H,PLBD1,C12orf60,SMCO3,ARHGDIB,RERG,GUCY2C
poultney_13_ASD_discovery_cases-case99HI1144B
Unknown
Unknown (likely multiplex/AGRE)
Unknown
ATF7IP,PLBD1
poultney_13_ASD_discovery_cases-case99HI1144B
Unknown
Unknown (likely multiplex/AGRE)
Unknown
RPL13AP20,MIR614,HTR7P1,APOLD1,DDX47,GPRC5A,GPRC5D,GPRC5D-AS1,HEBP1,FAM234B
prasad_12_ASD_discovery_cases-case117372L
Unknown
Unknown
Unknown
0 genes
prasad_12_ASD_discovery_cases-case83680L
Unknown
Unknown
Unknown
RPL13AP20
spataro_23_ASD/DD/ID_discovery_cases-case103
MLPA or aCGH
De novo
GRIN2B
wolfe_16_ID_discovery_cases-DECIPHER327120
qPCR, FISH, or QF-PCR
Unknown
Unknown
Unknown
GRIN2B
Controls
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
brandler_18_ASD_discovery_controls-controlSSC10629
Not available
Maternal
ATF7IP
poultney_13_ASD_discovery_controls-control05C44621
Unknown
HTR7P1,RNA5SP353,RNU6-590P,GSG1,EMP1,LINC01559,GPRC5D-AS1,HEBP1,FAM234B,GRIN2B
sanders_11_ASD_discovery_controls-11233.s1
Maternal
Simplex (quad)
NA
MRPS18CP4,RNU6-491P,GNAI2P1
No Animal Model Data Available