Severe microcephaly

Gene: NSD2

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 1:14 p.m. | Last Modified: 2 May 2024, 1:14 p.m.

Panel Version: 5.4

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: There is enough evidence for this gene to be green on this panel.

Created: 5 Dec 2023, 11:44 a.m. | Last Modified: 5 Dec 2023, 11:44 a.m.

Panel Version: 4.44

Microcephaly is well recognized as a feature associated with pathogenic NSD2 variants. PMID: 33941880 reports three NSD2 variants in three unrelated cases of Rauch-Steindl syndrome (OMIM:619695), who have severe microcephaly (Occipitofrontal circumference (OFC) below >3.0 SD). Similarly, PMID: 33276791 reports a case with
OFC of 44 cm (<−3SD). Further cases are examined in the supplementary table 4 in PMID: 33941880

Created: 5 Dec 2023, 11:42 a.m. | Last Modified: 5 Dec 2023, 1:48 p.m.

Panel Version: 4.44

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There are >3 unrelated cases associated with this gene; however, the severity of microcephaly in these cases do not satisfy our criteria for severe microcephaly. Therefore, this gene has been given an Amber rating.

Created: 16 Sep 2021, 1:07 p.m. | Last Modified: 16 Sep 2021, 1:07 p.m.

Panel Version: 2.236

Green List (high evidence)

Microcephaly reported in 6 of 7 individuals with LOF variants in this gene.
Sources: Expert list

Created: 31 Aug 2020, 8:59 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
microcephaly; intellectual disability

Publications

• 30345613
• 31171569