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Skeletal dysplasia

Region: ISCA-37447-Loss

DLK1-MEG3 Intergenic Region Loss

Green List (high evidence)
Chromosome: 14
GRCh38 Position: 100724515-100833215
Haploinsufficiency Score: Sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
Triplosensitivity Score:
Required percent of overlap: 60%
Variant types: CNV Loss

1 review

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) has been agreed for the R104 Skeletal dysplasia panel as only Kagami-Ogata syndrome includes skeletal abnormalities.
Created: 26 Feb 2025, 10:46 a.m. | Last Modified: 26 Feb 2025, 10:46 a.m.
Panel Version: 7.25
Multiple unrelated cases curated in ClinGen - sufficient evidence to add this region (https://search.clinicalgenome.org/kb/gene-dosage/region/ISCA-37447)

DLK1-MEG3 Intergenic Region includes the paternally expressed DLK1 gene, the 2 differentially methylated regions (DMRs) DLK1/MEG3:IG-DMR and MEG3:TSS-DMR, and the 5' end of the maternally expressed gene MEG3 (4 exons).

The phenotype depends on the parental origin: Kagami Ogata syndrome/KOS (maternally derived imprinting) or Temple syndrome/TS (paternally derived imprinting)

Kagami-Ogata syndrome is characterized by typical facial features, skeletal abnormalities (including ""coat-hanger ribs"", and bell-shaped thorax), abdominal wall defects, and developmental delay.

Temple syndrome is a less specific phenotype including intrauterine and postnatal growth restriction, hypotonia, feeding difficulties in infancy, truncal obesity, and small feet and hands.
Sources: ClinGen
Created: 26 Feb 2025, 10:25 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)

Phenotypes
Kagami-Ogata syndrome, OMIM:608149; Temple syndrome, OMIM:616222

Publications

Created: 26 Feb 2025, 10:25 a.m.

Panel version: 7.26

Details

ISCA ID
ISCA-37447-Loss
ISCA Region Name
DLK1-MEG3 Intergenic Region Loss
Chromosome
14
GRCh38 Coordinates
100724515-100833215
Haploinsufficiency Score
Sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
Triplosensitivity Score
Required percent of overlap
60%
Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Sources
  • Expert Review Green
  • ClinGen
Phenotypes
  • Kagami-Ogata syndrome, OMIM:608149
  • Temple syndrome, OMIM:616222
Clinvar variants
Variants in
Penetrance
None
Variant types
CNV Loss
Publications

History Filter Activity

26 Feb 2025, Gel status: 3

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Region: isca-37447-loss has been classified as Green List (High Evidence).

26 Feb 2025, Gel status: 1

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for Region: ISCA-37447-Loss was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)

26 Feb 2025, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Region: ISCA-37447-Loss was added Region: ISCA-37447-Loss was added to Skeletal dysplasia. Sources: ClinGen Mode of inheritance for Region: ISCA-37447-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for Region: ISCA-37447-Loss were set to 20585555; 24801763; 27406249; 33579810; 18176563; 28640239 Phenotypes for Region: ISCA-37447-Loss were set to Kagami-Ogata syndrome, OMIM:608149; Temple syndrome, OMIM:616222 Review for Region: ISCA-37447-Loss was set to GREEN