4q25-q26CNV Type: Duplication
Largest CNV size: 747246 bp
Statistics Box:
Number of Reports: 8
Number of Reports: 8
Summary Information
Rare singleton duplication within this region was found in a case from a study of 15,749 individuals from the International Standards for Cytogenomic Arrays (ISCA) consortium with unexplained developmental delay, intellectual disability, dysmorphic features, multiple congenital anomalies, autism spectrum disorders, or clinical features suggestive of a chromosomal syndrome (Kaminsky et al., 2011).
Additional Locus Information
References
Major Reports
Title
Author, Year
Report Class
CNV Type
An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabili...
Duplication
Rare Inherited and De Novo CNVs Reveal Complex Contributions to ASD Risk in Multiplex Families.
Duplication
Minor Reports
Title
Author, Year
Report Class
CNV Type
Identification of small exonic CNV from whole-exome sequence data and application to autism spectrum disorder.
Deletion
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
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_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
318348
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
747246
0
1
1
leppa_16_ASD_discovery_cases
Children affected with ASD from 1,464 families from the Autism Genetic Resource Exchange (AGRE)
1764
Diagnosis according to ADOS and ADI-R
N/A
N/A
4017000
0
1
1
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
3600000
1
0
1
miyake_23_ASD_discovery_cases
Cohort of ASD probands consisting of 351 trios, 24 quads, and two quintets included in a multi-center cohort.
405
Cases were clinically diagnosed with ASD based on DSM-V.
NA
69.88% Male
1016709
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)
176012
1
0
1
teunissen_23_ASD/DD/ID_discovery_cases
Individuals with microdeletions affecting the ANK2 gene from an initial cohort of 12 individuals with heterozygous ANK2 variation.
2
Both cases presented with autism spectrum disorder (ASD); one case also presented with mild developmental delay/intellectual disability.
Range, 9-12 yrs.
Female
318001
1
0
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
317999
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
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
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
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
leppa_16_ASD_discovery_cases
N/A
Solid phase hybridization
Illumina 550v1 and 550v3, Omni-1.0-B and -H, Omni 2.5
PennCNV, QuantiSNP, GNOSIS
GenomeStudio, CNVision
qPCR
maini_18_ASD/DD/ID_discovery_cases
Italian
aCGH, array SNP
Multiple platforms, including Agilent and Affymetrix arrays (8x60K oligochips since 2012)
None
miyake_23_ASD_discovery_cases
Japan
Exome sequencing
Illumina HiSeq 2000/2500
NA
XHMM
None
poultney_13_ASD_discovery_cases
European
WES
Agilent SureSelect Human All Exon v.2
XHMM
None
teunissen_23_ASD/DD/ID_discovery_cases
NA
CMA, WES
NA
NA
NA
None
yuen_17_ASD_discovery_cases
N/A
WGS
Complete Genomics, Illumina HiSeq 2000, HiSeq X
None (CNV validation not available, CNV not detected by validation method, or CNV not detected by WGS but was detected by validation methodology)
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
poultney_13_ASD_discovery_controls
European
WES
Agilent SureSelect Human All Exon v.2
XHMM
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-caseAU3728301
N/A
F
ASD
Case from MSSNG cohort
112983776
113302123
318348
GRCh38
Deletion
No
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00000992
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
112689224
113436470
747247
GRCh38
Duplication
Yes
leppa_16_ASD_discovery_cases-AU1483301
N/A
N/A
ASD
112937085
116954105
4017021
GRCh38
Duplication
Yes
maini_18_ASD/DD/ID_discovery_cases-case35
11 yrs.
M
Intellectual disability
Birth history: born at 40 weeks gestation, no reported pregnancy anomalies. Developmental milestones: no language delay or motor delay. Language and communication evaluation: no language disorder or absent speech. Behavioral/psychiatric evaluation: positive for psychiatirc illness. Epilepsy/abnormal EEG: positive for epilepsy and/or abnormal EEG. Additional medical history: skin softness/joint laxity. Dysmorphic features: no reported dysmorphic features. Growth parameters: normal head circumference, normal growth. Family history: negative for consanguineity, positive for familiarity, family history positive for NDDs.
Moderate intellectual disability
112147094
115760076
3612983
GRCh38
Deletion
No
miyake_23_ASD_discovery_cases-case10683
NA
M
ASD
Case clinically diagnosed with ASD based on DSM-V criteria.
112514625
113531333
1016709
GRCh38
Deletion
No
poultney_13_ASD_discovery_cases-case01HI2071A
N/A
F
ASD
ASD case from AGRE (AGRE ID AU0045301; NDAR ID NDAR_INVJA948WDK)
113106863
113282874
176012
GRCh38
Deletion
No
teunissen_23_ASD/DD/ID_discovery_cases-case7
9 yrs.
F
ASD
Behavioral/psychiatric evaluation: autism spectrum disorder.
112983844
113301844
318001
GRCh38
Deletion
No
yuen_17_ASD_discovery_cases-caseAU3728301
N/A
N/A
ASD
Case cohort: AGRE. Clinical description: N/A
112983845
113301844
318000
GRCh38
Deletion
No
Controls
No Control Data Available
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
brandler_18_ASD_replication_cases-caseAU3728301
No validation step reported
De novo
MIR1243,MIR8082,ANK2
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00000992
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
WRBP1,RPL7AP30,MIR1243,MIR8082,RN7SL184P,RNU1-138P,ANK2
leppa_16_ASD_discovery_cases-AU1483301
qPCR
De novo
Unknown
Possibly segregated
MIR1243,MIR8082,RN7SL184P,RNU1-138P,MIR577,CIR1P2,RN7SL808P,MRPS33P3,RPF2P2,PGAM4P2,KRT18P21,EIF3KP3,TTC39CP1,MTRNR2L13,MIR1973,TRMT112P1,CUL4AP1,ACTN4P1,RNU6-119P,UGT8,CAMK2D,ARSJ,NDST4,ANK2
maini_18_ASD/DD/ID_discovery_cases-case35
Paternal
Not simplex
Unknown
RTEL1P1,TOX4P1,NEUROG2,RPL23AP94,MIR367,MIR302D,MIR302A,MIR302C,MIR302B,OSTCP4,WRBP1,RPL7AP30,MIR1243,MIR8082,RN7SL184P,RNU1-138P,MIR577,CIR1P2,RN7SL808P,MRPS33P3,RPF2P2,FAM241A,AP1AR,TIFA,LARP7,UGT8,ALPK1,ZGRF1,CAMK2D,ARSJ,NDST4,ANK2
miyake_23_ASD_discovery_cases-case10683
Unable to be validated due to limited residual DNA samples
De novo
ANK2,CAMK2D,LARP7,ZGRF1,NEUROG2,GET1P1,RPL7AP30,MIR302A,MIR302C,MIR367,MIR302D,MIR302B,OSTCP4,RPL32P13,MIR1243,MIR8082,ANK2-AS1,NEUROG2-AS1,RN7SL184P,RNU1-138P,RPL23AP94,H3P14,MIR302CHG
poultney_13_ASD_discovery_cases-case01HI2071A
Unknown
Unknown (likely multiplex/AGRE)
Unknown
MIR1243,MIR8082,ANK2
teunissen_23_ASD/DD/ID_discovery_cases-case7
De novo
ANK2,MIR1243,MIR8082,ANK2-AS1
yuen_17_ASD_discovery_cases-caseAU3728301
Not available
De novo
Simplex
Segregated
MIR1243,MIR8082,ANK2
Controls
No Control Data Available
No Animal Model Data Available