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  3. ISCA-37433-Loss
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Early onset or syndromic epilepsy

Region: ISCA-37433-Loss

22q11.2 recurrent (DGS/VCFS) region (proximal, A-B) (includes TBX1) Loss

Green List (high evidence)
Chromosome: 22
GRCh38 Position: 18924718-20299685
Haploinsufficiency Score: Sufficient evidence suggesting dosage sensitivity is associated with clinical phenotype
Triplosensitivity Score:
Required percent of overlap: 60%
Variant types: CNV Loss

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: This region has been deprecated by ClinGen and therefore should be removed from the panel.

This region has been subsumed into ISCA-37446 which is green on multiple GMS panels including this panel (https://panelapp.genomicsengland.co.uk/panels/entities/ISCA-37446-Loss)

Checked and approved by the Genomics England Clinical team.
Created: 12 Nov 2025, 4:13 p.m. | Last Modified: 12 Nov 2025, 4:13 p.m.
Panel Version: 8.66
The required percent of overlap for this region has been changed from 80% to 60% and the genomic location has been updated inline with ClinGen following NHS Genomic Medicine Service approval.
Created: 16 Mar 2022, 1:10 p.m. | Last Modified: 16 Mar 2022, 1:10 p.m.
Panel Version: 2.500
Created: 16 Mar 2022, 1:10 p.m.
Last Modified: 16 Mar 2022, 1:10 p.m.
Panel version: 2.500

Rebecca Foulger (Genomics England curator)

PMID:30977115: Eaton et al., 2019: Overall, 11% (12/108) of deletion carriers had an epilepsy diagnosis. 57/96 remaining deletion carriers (59.4%) had seizures or seizure-like symptoms (including febrile seizures). Most patients with 22q11.2 deletion syndrome had either deletion type A-D (ISCA-37446 75.9%) or deletion type A-B (ISCA-37433 6.5% 7/108 patients)- see Table 1.
Created: 14 Oct 2019, 10:14 a.m. | Last Modified: 14 Oct 2019, 10:14 a.m.
Panel Version: 1.364
Added CNV to panel on recommendation from Alisdair McNeill (SHEFFIELD CHILDREN'S NHS FOUNDATION TRUST) who notes that "Multiple case series demonstrate 22q11.2 deletion syndrome is associated with epilepsy, e.g. PubMed:30977115" (personal communication via email, October 7th 2019).
Created: 14 Oct 2019, 10:11 a.m. | Last Modified: 14 Oct 2019, 10:11 a.m.
Panel Version: 1.364

Phenotypes
Epilepsy; seizures; seizure-like symptoms

Publications

Created: 14 Oct 2019, 10:08 a.m.
Last Modified: 14 Oct 2019, 10:08 a.m.
Panel version: 1.364

Details

ISCA ID
ISCA-37433-Loss
ISCA Region Name
22q11.2 recurrent (DGS/VCFS) region (proximal, A-B) (includes TBX1) Loss
Chromosome
22
GRCh38 Coordinates
18924718-20299685
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 Green
  • ClinGen
Phenotypes
  • Learning difficulties
  • immune deficiency
  • renal anomalies
  • cleft palate, polydactyly
  • 22q11.2 deletion syndrome
  • diaphragmatic hernia
  • 192430
  • polyhydramnios
  • DiGeorge syndrome
  • Velocardiofacial syndrome
  • 188400
  • facial dysmorphic features, high frequency of cardiac defects, including conotruncal defects, prematurity, growth restriction, microcephaly, and mild developmental delay
  • congenital heart disease
Tags
Q3_25_demote_red
Clinvar variants
Variants in
Penetrance
None
Variant types
CNV Loss
Publications

History Filter Activity

12 Nov 2025, Gel status: 3

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Region: isca-37433-loss has been classified as Green List (High Evidence).

12 Nov 2025, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_25_demote_red tag was added to Region: ISCA-37433-Loss.

16 Mar 2022, Gel status: 3

Changed GRCh38, Changed Required Overlap Percentage

Arina Puzriakova (Genomics England Curator)

GRCh38 position for ISCA-37433-Loss was changed from 18924718-20299686 to 18924718-20299685. Required Overlap Percentage for ISCA-37433-Loss was changed from 80 to 60.

14 Oct 2019, Gel status: 3

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

Rebecca Foulger (Genomics England curator)

Region: ISCA-37433-Loss was added Region: ISCA-37433-Loss was added to Genetic epilepsy syndromes. Sources: ClinGen,Expert Review Green Mode of inheritance for Region: ISCA-37433-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for Region: ISCA-37433-Loss were set to 15545748; 15889418; 20301696 Phenotypes for Region: ISCA-37433-Loss were set to Learning difficulties; immune deficiency; renal anomalies; cleft palate, polydactyly; 22q11.2 deletion syndrome; diaphragmatic hernia; 192430; polyhydramnios; DiGeorge syndrome; Velocardiofacial syndrome; 188400; facial dysmorphic features, high frequency of cardiac defects, including conotruncal defects, prematurity, growth restriction, microcephaly, and mild developmental delay; congenital heart disease