Fetal anomalies
Gene: HECW2

HECW2 (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2)
EnsemblGeneIds (GRCh38): ENSG00000138411
EnsemblGeneIds (GRCh37): ENSG00000138411
OMIM: 617245, Gene2Phenotype
HECW2 is in 6 panels

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Red List (low evidence)

Clinical presentation is typically post-natal.

Typically denovo missense variants in the HECT domain.
PMID: 29807643 - R1191Q single case with severe D/ID, EE and regression
PMID: 29395664 - single case with regression, loss of swallowing, increased abnormal movements/hand stereotypies, Rett like, cortical visual impairment and EE
PMID: 27334371 - propose GOF or dominant negative; 1 case plus references 5 previous cases
PMID: 27389779 - four novel de novo predicted deleterious missense variants in HECW2 in six probands with ID/developmental delay and hypotonia. Other common features include seizures, strabismus, nystagmus, cortical visual impairment and dysmorphic facial features. p. Arg1330Trp, p.Glu1445Gly reported >1 case.
Regression reported in the context of refractory EE
Created: 19 Oct 2020, 4:12 a.m. | Last Modified: 18 Feb 2022, 5:16 a.m.

Panel Version: 0.3697

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder with hypotonia, seizures, and absent language, MIM# 617268; intellectual disability; epilepsy; regression; microcephaly

Publications

Mode of pathogenicity
Other

Created: 19 Oct 2020, 4:12 a.m.
Last Modified: 18 Feb 2022, 5:16 a.m.
Panel version: 0.3697

Teresa Zhao (Victorian Clinical Genetics Services)

Green List (high evidence)

Only missense reported to date which clustered towards the HECW domain or the C-terminal part of the protein.

Mostly de novo.
Created: 8 Sep 2020, 12:45 a.m. | Last Modified: 8 Sep 2020, 12:45 a.m.

Panel Version: 0.2976

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

Phenotypes
Neurodevelopmental disorder with hypotonia, seizures, and absent language (MIM#617268)

Publications

27389779

Created: 8 Sep 2020, 12:45 a.m.
Last Modified: 8 Sep 2020, 12:45 a.m.
Panel version: Imported from Intellectual disability syndromic and non-syndromic panel version 0.2976

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Red
Genomics England PanelApp
Genetic Health Queensland

Phenotypes

Neurodevelopmental disorder with hypotonia, seizures, and absent language (MIM#617268)

OMIM

617245

Clinvar variants

Variants in HECW2

Penetrance

None

Publications

Mode of Pathogenicity

Other

Panels with this gene