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Intellectual disability

Region: ISCA-46300-Loss

15q24 recurrent region (LCR C-LCR D) (includes SIN3A) Loss

Amber List (moderate evidence)
Chromosome: 15
GRCh38 Position: 75339446-75680568
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 list classification: This region has Sufficient Evidence for Haploinsufficiency in ClinGen and should be promoted to Green at the next GMS panel update.

Panel inclusion has been reviewed and approved by the Genomics England Clinical team.
Created: 12 Nov 2025, 3:44 p.m. | Last Modified: 12 Nov 2025, 3:44 p.m.
Panel Version: 9.169
https://search.clinicalgenome.org/kb/gene-dosage/region/ISCA-46300

ClinGen review (Last Evaluated:10/24/2025): Deletion of the 15q24 recurrent region (C-D) has been reported in at least 4 patients with a syndromic clinical phenotype characterized by developmental delays (speech and motor), intellectual disability, brain anomalies, craniofacial abnormalities, hypermobile joints, digital findings, and other variable clinical features. Two additional patients have also been reported with atypical deletions encompassed by the 15q24 LCR C-D region, but with breakpoints proximal to LCR D. Both of these patients had a similar clinical presentation to patients with the typical 15q24 LCR C-D deletion. Parental studies have demonstrated that each of the deletions in this region (6 total) represent de novo events. Case-control data are currently uninformative due to the rarity of this deletion. The known haploinsufficient gene SIN3A is thought to represent the critical gene within this region, as SIN3A sequence level have a similar clinical presentation to recurrent deletion.
Sources: ClinGen
Created: 12 Nov 2025, 3:39 p.m. | Last Modified: 12 Nov 2025, 3:39 p.m.
Panel Version: 9.168

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Developmental delays/intellectual disability, brain anomalies, craniofacial abnormalities, hypermobile joints, digital findings, and other variable clinical features

Publications

Created: 12 Nov 2025, 3:39 p.m.
Last Modified: 12 Nov 2025, 3:39 p.m.
Panel version: 9.168

Details

ISCA ID
ISCA-46300-Loss
ISCA Region Name
15q24 recurrent region (LCR C-LCR D) (includes SIN3A) Loss
Chromosome
15
GRCh38 Coordinates
75339446-75680568
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, imprinted status unknown
Sources
  • Expert Review Amber
  • ClinGen
Phenotypes
  • Developmental delays/intellectual disability, brain anomalies, craniofacial abnormalities, hypermobile joints, digital findings, and other variable clinical features
Tags
Q3_25_promote_green
Clinvar variants
Variants in
Penetrance
None
Variant types
CNV Loss
Publications

History Filter Activity

12 Nov 2025, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Region: isca-46300-loss has been classified as Amber List (Moderate Evidence).

12 Nov 2025, Gel status: 1

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

Arina Puzriakova (Genomics England Curator)

Region: ISCA-46300-Loss was added Region: ISCA-46300-Loss was added to Intellectual disability. Sources: ClinGen Q3_25_promote_green tags were added to Region: ISCA-46300-Loss. Mode of inheritance for Region: ISCA-46300-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for Region: ISCA-46300-Loss were set to 27399968; 22180641 Phenotypes for Region: ISCA-46300-Loss were set to Developmental delays/intellectual disability, brain anomalies, craniofacial abnormalities, hypermobile joints, digital findings, and other variable clinical features Review for Region: ISCA-46300-Loss was set to GREEN