Table 2 Summary of confirmed de novo CNVs identified in genes/loci not previously associated with ID and summary of patient phenotype and other CMA information

From: Single exon-resolution targeted chromosomal microarray analysis of known and candidate intellectual disability genes

Patient ID

CNV

Minimum size (Maximum size) Kb

Gene within Min Region (MIM #)

Minimum gene region affected

Expected effect of CNV on protein a

Patient phenotype

DGV entries mapping to coding region of named gene(s)

Clinical or research CMA result

413

chr1.hg18:g.(233,491,105_233,556,700)_(233,557,700_233,560,656)dup

1.0 (69.6)

ARID4B (609696)

Exons 1,2

No frame-shift with tandem duplication

ID, autism

DGV #48278 gain variant, begins upstream of gene and includes up to exon 7 of gene.

 

543

chr2.hg18:g.(86,535,860_86,537,100)_(86,537,200_86,537,443)dup

0.3 (74.1)

KDM3A (611512)

Exon 6

Frameshift/premature STOP

ID

None.

Normal (105 K Gene DX)

447

chr2.hg18:g.(209,997,540_210,080,600)_(210,306,600_213,110,930)del

226 (3113)

MAP2 (157130)

Whole gene

Whole-gene deletion

ID, autism

One small variant mapping to intron of MAP2

 

839

chr2.hg18:g.(853,846_895,990)_(896,180_935,391)del

0.02 (81.5)

SNTG2 (608715)

1 kb upstream

Involves predicted promoter

N/A

Many

 

164

chr3.hg18:g.(53,954,275_85,100,000)_(86,000,000_121,027,757)del

0.9 (67073.5)

CADM2 (609938)

Whole gene

Whole-gene deletion

Global developmental delay

DGV #53089 is an 88 Kb loss in 2 individuals

 

513b

chr4.hg18:g.(5,874,387_5,908,550)_(5,908,900_6,114,729)del

0.35 (240.3)

CRMP1 (602462)

Whole gene

Whole-gene deletion

ID, autism

11 small DGV entries in maximally affected region, 1 affects coding sequence, rest are intronic/non-genic

 

391

chr6.hg18:g.(15,568,665_15,576,500)_(15,577,250_15,595,501)del

0.8 (26.8)

JARID2 (601594)

Exon 6

Deletion/tandem duplication does not cause a frame-shift. Exon 6 codes a low complexity motif without known function

ID, short stature, ASD

None

 

9390

chr6.hg18:g.(15,568,665_15,576,500)_(15,577,250_15,595,501)del

0.8 (26.8)

JARID2

Exon 6

 

ID, CL/P, deafness, facial dysmorphisms

  

901

chr6.hg18:g.(15,568,665_15,576,500)_(15,577,250_15,595,501)del

0.8 (26.8)

JARID2

Exon 6

 

ID, overgrowth

  

931b

chr6.hg18:g.(15,568,665_15,576,500)_(15,577,250_15,595,501)del

0.8 (26.8)

JARID2

Exon 6

 

ID, spasticity, epilepsy, acquired microcephaly

  

268

chr6.hg18:g.(15,568,665_15,576,500)_(15,577,250_15,595,501)del

0.8 (26.8)

JARID2

Exon 6

 

ID, autism

  

490

chr6.hg18:g.(15,568,665_15,576,500)_(15,577,250_15,595,501)dup

0.8 (26.8)

JARID2

Exon 6

 

ID with ASD

  

341

chr6.hg18:g.(15,568,665_15,576,500)_(15,577,250_15,595,501)dup

0.8 (26.8)

JARID2

Exon 6

 

ID with minor facial dysmorphisms

  

141

chr8.hg18:g(22,048,373_24,826,912)_(24,832,700_26,491,057)del

5.8 (4442.7)

NEFM (162250)

Whole gene

Whole-gene deletion

ID

None in affected exons but several in maximally affected region

 

600b

chr10.hg18:g.(64,647,390_64,698,700)_(64,699,000_64,721,535)dup

0.3 (74.1)

JMJD1C (604503)

Exon 4

Discrepancy of exon size from source curation. Manual curation: no frameshift. Alamut curation: Frameshift/premature STOP

Non-syndromic ID

None

 

7484

chr12.hg18:g.(44,409,886_44,409,000)_(44,412,000_44,588,086)dup

3.0 (178.2)

ARID2 (609539)

Exons 1,2,3 (6 copy gain by qPCR)

Effect of six copy gain unpredictable. Single-tandem duplication causes frame-shift and premature STOP

ID, facial dysmorphism, short stature, unilateral deafness

DGV # 3887 gain variant begins before exon 3 and extends beyond gene.

 

576

chr18.hg18:g.(23,982,030_24,010,750)_(24,011,500_37,690,792)del

0.8 (13708.8)

CDH2 (114020)

Exon 1,2

Removes transcriptional start site

Global developmental delay

None

 

7581

chr18.hg18:g.(23,982,030_24,010,750)_(24,011,500_37,690,792)del

0.8 (13708.8)

CDH2 (114020)

Exon 1,2

Removes transcriptional start site

ID, cleft lip/palate

See above

Normal (Affymetrix 500 K, Agilent 244 K, NimbleGen 385 K)

706

chr20.hg18:g.(39,613,550_39,680,100)_(39,680,750_39,688,521)del

0.7 (75.0)

CHD6

Exon 1

 

ID, autism, epilepsy

Two small variants mapped to introns.

Normal (BAC array Signature Genomics)

  1. Abbreviations: CMA, chromosomal microarray; CNV, copy-number variant; DGV, database of genomic variants. CNVs are reported as per Human Genome Variation Society guidelines. Minimal gene region affected refers to the gene content contained within the minimally deleted/duplication region. Minimal size is defined as the difference between the genomic coordinates of the last abnormal probe and the first abnormal probe, and the maximum size is defined as the difference between the genomic coordinates of the first normal probe ___location distal to the CNV and the last normal probe ___location proximal to the CNV. Exon numbering is according to the NCBI reference sequence database (RefSeq). http://dgvbeta.tcag.ca/gb2/gbrowse/dgv2_hg18/.
  2. aEffect on protein predicted using Alamut V2.2.
  3. bPatients with more than one CNV identified in this study.
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