15q24.2CNV Type: Deletion
Largest CNV size: 108000 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
A large-scale survey of the novel 15q24 microdeletion syndrome in autism spectrum disorders identifies an atypical deletion that narrows the critic...
Deletion
An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabili...
Deletion-Duplication
A discovery resource of rare copy number variations in individuals with autism spectrum disorder.
Deletion-Duplication
Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.
Deletion
Haploinsufficiency of MeCP2-interacting transcriptional co-repressor SIN3A causes mild intellectual disability by affecting the development of cort...
Deletion
Minor Reports
Title
Author, Year
Report Class
CNV Type
Rare structural variation of synapse and neurotransmission genes in autism.
Deletion
Identification of small exonic CNV from whole-exome sequence data and application to autism spectrum disorder.
Deletion
Performance of case-control rare copy number variation annotation in classification of autism.
Duplication
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_replication_cases
Affected individuals from MSSNG cohort (1395 cases from 1187 families) and the Simons Simplex 2 (SSC2) cohort (584 cases from simplex quad families)
1979
Cases diagnosed with ASD
N/A
N/A
16717
2
0
2
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
221177
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
108410
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
3389
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
452826
3
1
4
mcinnes_10_ASD_replication_cases
ASD cases from 785 families (291 simplex, 494 multiplex) from Autism Genetic Resource Exchange (AGRE).
1336
ASD
78.7% Male
108000
2
0
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)
78721
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
98305
1
2
3
witteveen_16_ASD/ID/EP_discovery_cases
Individuals with atypical 15q24 microdeletions containing the SIN3A gene; two individuals were ascertained during a clinical genetic diagnostic work-up because of unexplained intellectual disability at one of the involved genetic diagnostic services in Nijmegen, Groningen, Nantes, and Southampton, while an additional two individuals were recruited from the DECIPHER database.
4
All four cases presented with mild intellectual disability and dysmorphic facial features; one case also presented with ASD, while another presented with epilepsy.
Range, 3 yrs. 8 mos.-29 yrs.
25% Male
500000
4
0
4
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
52092
1
0
1
girirajan_13a_ASD_discovery_controls1
NIMH control cohort consisting of 207 DNA samples obtained from Rutgers Univ. Cell and DNA Repository, and 373 individuals from ClinSeq study of artherosclerotic disease
580
Control. Individuals from NIMH control cohort negative for DSM-IV criteria for major depression and history of bipolar disorder or psychosis.
NA
NA
0
0
0
0
girirajan_13a_ASD_discovery_controls2
Controls characterized through the Wellcome Trust Case-Control Consortium (WTCCC) for smaller hotspot regions and candidate-gene events
2090
Control
NA
NA
N/A
N/A
N/A
N/A
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
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)
98305
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.
33712
0
1
1
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
brandler_18_ASD_replication_cases
N/A
WGS
Illumina HiSeq X10
ForestSV, Lumpy, Manta, Mobster, SV2
None
engchuan_15_ASD_discovery_cases
Caucasian
Solid phase hybridization
Illumina 1M
None
gai_11_ASD_replication_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
aCGH (NimbleGen 135K array)
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
mcinnes_10_ASD_replication_cases
Solid phase hybridization
Illumina HumanHap550 BeadChip
qPCR
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
qPCR
witteveen_16_ASD/ID/EP_discovery_cases
N/A
aCGH
Agilent 105K, Agilent 8x60K ISCA
FISH
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_13a_ASD_discovery_controls1
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_13a_ASD_discovery_controls2
NA
Solid phase hybridization
Illumina 1.2M SNP microarray
None
kaminsky_11_DD/ID/ASD_discovery_controls
NA
aCGH
Agilent 44K, Agilent 105K
Feature Extraction, DNA Analytics
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
brandler_18_ASD_replication_cases-case1-1055-003
N/A
F
ASD
Case from MSSNG cohort
75472275
75488991
16717
GRCh38
Deletion
No
brandler_18_ASD_replication_cases-case1-1055-003
N/A
F
ASD
Case from MSSNG cohort
75574926
75578015
3090
GRCh38
Deletion
No
engchuan_15_ASD_discovery_cases-case14377_4900
N/A
N/A
ASD
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
75896407
76117584
221178
GRCh38
Duplication
No
gai_11_ASD_replication_cases-AU058003
Autism
75832232
75940641
108410
GRCh38
Deletion
No
girirajan_13a_ASD_discovery_cases-AU1228303
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
76214887
76218276
3390
GRCh38
Deletion
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002090
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
75336215
75658670
322456
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002309
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
75432164
75626896
194733
GRCh38
Deletion
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00003782
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
75307767
75727625
419859
GRCh38
Deletion
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00004249
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
75596961
76049787
452827
GRCh38
Deletion
Yes
mcinnes_10_ASD_replication_cases-AU058-003
NA
M
Broad spectrum
NA
NA
75832232
75940641
108410
GRCh38
Deletion
Yes
mcinnes_10_ASD_replication_cases-AU058-004
NA
M
Autism
NA
NA
75832232
75940641
108410
GRCh38
Deletion
Yes
poultney_13_ASD_discovery_cases-case99HI0944
N/A
M
ASD
ASD case from AGRE (AGRE ID AU058003; NDAR ID NDAR_INVGK583YBV)
75854384
75933104
78721
GRCh38
Deletion
No
prasad_12_ASD_discovery_cases-case114961L
NA
M
ASD
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS. Novel CNV
73443582
73460490
16909
Unknown
Duplication
No
prasad_12_ASD_discovery_cases-case123295
NA
M
ASD
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS. CNV identified by previous SNP microarray study
73661681
73759985
98305
Unknown
Duplication
No
prasad_12_ASD_discovery_cases-case62261L
NA
M
ASD
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS. Novel CNV
73636914
73649849
12936
Unknown
Deletion
Yes
witteveen_16_ASD/ID/EP_discovery_cases-case1
29 yrs.
F
ASD and intellectual disability
Birth/neonatal history: pregnancy complicated by IUGR since 20 weeks; born preterm at 36 weeks with birth weight of 1140 g (
Mild intellectual disability
75307659
75807659
500001
GRCh38
Deletion
No
witteveen_16_ASD/ID/EP_discovery_cases-case2
4 yrs. 9 mos.
F
Intellectual disability and epilepsy
Birth/neonatal history: pregnancy complicated by maternal hypertension at 38 weeks; born at 39+6 weeks afted induced but uncomplicated birth; birth weight 3250 g (25th %ile) and head circumference of 34 cm (5th-10th %ile). Developmental milestones: delayed motor development (walking with support at 18 months); mildly delayed cognitive development. Motor, muscular, and skeletal evaluation: 2nd toes were positioned crossing the 3rd toes. Epilepsy/seizures: developed seizures in first year that were successfully treated with valproic acid. Brain imaging: irregular aspect of the cortex in the frontal regions, corpus callosum dysgenesis, delayed myelination. Dysmorphic features: downslanted palpebreal fissures, deeply set eyes, small mouth, broad and overhanging nasal tip. Growth parameters: height of 86.5 cm (25th %ile), weight of 11.16 kg (10th %ile), and head circumference of 45.3 cm (3rd %ile) at age of 2 years 1 month.
Mild intellectual disability
75307659
75807659
500001
GRCh38
Deletion
No
witteveen_16_ASD/ID/EP_discovery_cases-case3
4 yrs. 9 mos.
F
Intellectual disability
Birth/neonatal history: born at 35 weeks gestation following spontaneous rupture of membranes; birth weight of 1950 g (<16th %ile; normal twin had a birth weight of 2070 g); developed jaundice on day four and was admitted for phototherapy, requiring a 5-day hospital stay. Developmental milestones: slight delay in early developmental milestones (sitting at 8 months, walking at 18 months); delay in expressive speech, but was felt to have caught up tp age-appropriate levels by 4 years of age. Motor, muscular, and skeletal evaluation: significant fine motor problems resulting in poor pencil grip, immature writing and difficulties holding cutlery; need for supportive orthotic boots for ankle hypermobility; generalized joint hypermobility. Behavioral/psychiatric evaluation: age-appropriate social skills; episode of anxiety at age of 4 years, resulting in hair-pulling and causing a bald patch. Brain imaging: not performed. Visual evaluation: mild hypermetropia with a prescription of +2 diopters bilaterally. Additional medical history: recurrent glue ear and tonsillitis with sleep apnea requiring a tonsillectomy; frequent urinary tract infections. Dysmorphic features: broad and tall forehead, short palpebral fissures with shallow orbits, very low nasal bridge, small nose, small mouth, pointed chin. Growth parameters: height of 96.8 cm (5th %ile), weight of 15.4 kg (50th %ile), and head circumference of 48 cm (10th %ile). Family history: case is one of two naturally conceived, non-identical female twins (her sister is unaffected).
Mild intellectual disability
75307659
75727659
420001
GRCh38
Deletion
No
witteveen_16_ASD/ID/EP_discovery_cases-case4
3 yrs. 8 mos.
M
Intellectual disability
Birth/neonatal history: born at term with normal birth weight (3280 g, 50th %ile); feeding difficulties due to GERD during first months. Developmental milestones: slight motor delay (sitting at 9 months, walking at 21 months); mildly delayed speech development (first words at 2 years, began to use short simple sentences at 3 years 8 months). Langauge and communication evaluation: comprehension of spoken language better than expression. Behavioral/psychiatric evaluation: unremarkable behavior. Brain imaging: not performed. Visual evaluation: normal. Auditory evaluation: normal. Dysmorphic features: triangular face, broad and high forehead, downslanted palpebral fissures, epicanthic folds, small mouth, pointed chin. Growth parameters: height of 49.4 cm (25th %ile), weight of 13.8 kg (16th %ile), and head circumference of 49.4 cm (25th %ile) at age of 3 years 8 months.
Mild intellectual disability
75307659
75657659
350001
GRCh38
Deletion
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
engchuan_15_ASD_discovery_controls-controlB703785_1007873472
N/A
N/A
Control
No previous psychiatric history
75960209
76012301
52093
GRCh38
Deletion
No
sanders_11_ASD_discovery_controls-11421.s1
8.7
F
Control (matched sibling)
NA
NA
75123621
75157333
33713
GRCh38
Duplication
No
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
brandler_18_ASD_replication_cases-case1-1055-003
No validation step reported
Paternal
PTPN9
brandler_18_ASD_replication_cases-case1-1055-003
No validation step reported
Maternal
PTPN9
engchuan_15_ASD_discovery_cases-case14377_4900
Unknown
FBXO22,UBE2Q2,NRG4,TMEM266
gai_11_ASD_replication_cases-AU058003
Inherited
RN7SL510P,FBXO22,UBE2Q2,NRG4
girirajan_13a_ASD_discovery_cases-AU1228303
aCGH (NimbleGen 135K array)
Paternal
Multiplex
Unknown
TMEM266,ETFA
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002090
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
COMMD4,MIR631,RPL13P4,NEIL1,SIN3A,SNUPN,IMP3,SNX33,MAN2C1,PTPN9
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002309
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
De novo
Unknown
Unknown
SIN3A,SNUPN,PTPN9
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00003782
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
ANP32BP1,COMMD4,MIR631,RPL13P4,NEIL1,SIN3A,SNUPN,IMP3,SNX33,CSPG4,ODF3L1,MAN2C1,PTPN9
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00004249
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
DNM1P35,PPIAP47,MIR4313,RN7SL319P,RN7SL510P,SNUPN,IMP3,SNX33,CSPG4,ODF3L1,DNM1P49,FBXO22,UBE2Q2,NRG4
mcinnes_10_ASD_replication_cases-AU058-003
qPCR
Paternal
Multiplex
Possibly segregated
RN7SL510P,FBXO22,UBE2Q2,NRG4
mcinnes_10_ASD_replication_cases-AU058-004
qPCR
Paternal
Multiplex
Possibly segregated
RN7SL510P,FBXO22,UBE2Q2,NRG4
poultney_13_ASD_discovery_cases-case99HI0944
Unknown
Unknown (likely multiplex/AGRE)
Unknown
RN7SL510P,FBXO22,UBE2Q2
prasad_12_ASD_discovery_cases-case114961L
Unknown
Unknown
Unknown
MAN2C1,SIN3A
prasad_12_ASD_discovery_cases-case123295
Unknown
Unknown
Unknown
IMP3,SNX33,SNUPN,CSPG4
prasad_12_ASD_discovery_cases-case62261L
qPCR
Paternal
Unknown
Unknown
PTPN9
witteveen_16_ASD/ID/EP_discovery_cases-case1
De novo
ANP32BP1,COMMD4,MIR631,RPL13P4,DNM1P35,PPIAP47,MIR4313,RN7SL319P,NEIL1,SIN3A,SNUPN,IMP3,SNX33,CSPG4,ODF3L1,DNM1P49,MAN2C1,PTPN9
witteveen_16_ASD/ID/EP_discovery_cases-case2
De novo
ANP32BP1,COMMD4,MIR631,RPL13P4,DNM1P35,PPIAP47,MIR4313,RN7SL319P,NEIL1,SIN3A,SNUPN,IMP3,SNX33,CSPG4,ODF3L1,DNM1P49,MAN2C1,PTPN9
witteveen_16_ASD/ID/EP_discovery_cases-case3
De novo
Simplex
ANP32BP1,COMMD4,MIR631,RPL13P4,NEIL1,SIN3A,SNUPN,IMP3,SNX33,CSPG4,ODF3L1,MAN2C1,PTPN9
witteveen_16_ASD/ID/EP_discovery_cases-case4
FISH
De novo
ANP32BP1,COMMD4,MIR631,RPL13P4,NEIL1,SIN3A,SNUPN,IMP3,SNX33,MAN2C1,PTPN9
Controls
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
engchuan_15_ASD_discovery_controls-controlB703785_1007873472
Unknown
NRG4
sanders_11_ASD_discovery_controls-11421.s1
Maternal
Simplex (quad)
NA
No Animal Model Data Available