Severe microcephaly

Region: ISCA-46300-Loss

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

I don't know

Comment on list classification: This region has Sufficient Evidence for Haploinsufficiency in ClinGen, however, microcephaly reported in patients is often now within the severity range relevant to this panel (OFC reported in 27399968; 22180641: 10-15th, 0.6-2nd, 3rd, 10th percentile) so will include as Amber based on this evidence.

Created: 12 Nov 2025, 3:43 p.m. | Last Modified: 12 Nov 2025, 3:43 p.m.

Panel Version: 8.19

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, 3:40 p.m.

Panel Version: 8.18

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

• 27399968
• 22180641