Genes in panel
STRs in panel
Prev Next

Severe microcephaly

Gene: TNPO2

Amber List (moderate evidence)

TNPO2 (transportin 2)
EnsemblGeneIds (GRCh38): ENSG00000105576
EnsemblGeneIds (GRCh37): ENSG00000105576
OMIM: 603002, Gene2Phenotype
TNPO2 is in 3 panels

1 review

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are sufficient unrelated cases presenting were a relevant phenotype associated with variants in this gene to rate as Green at the next GMS panel update.
Created: 23 Sep 2021, 10:04 a.m. | Last Modified: 23 Sep 2021, 10:04 a.m.
Panel Version: 2.250
Goodman et al., 2021 (PMID: 34314705) reported on 15 unrelated individuals with different variants in this gene (14 de novo, 1 mosaic in mother; 12 SNVs, 3 in-frame deletions, 1 deletion-insertion). All had GDD and all those who were assessed also had ID (9/9), ranging from mild to severe. ID also suspected but not investigated in another 3 cases. 6 had seizures starting between 1 and 2.5 years of age. 5 individuals had microcephaly (HC ranging -2.77 to -4.53 SD). Other less common features were also observed such as variable brain, gastrointestinal and ophthalmologic abnormalities.

Notably 6 individuals had additional SNVs/CNVs of uncertain significance, some of which include known ID genes (e.g. SETBP1, CUX2, ARMC9, PDE4D), but were discounted due to lack of explanation of the overall patient phenotype.

Some functional studies conducted in Drosophila demonstrated that patient-associated variants caused neurodevelopmental defects that were dosage and location (of variant within protein) dependent.
Sources: Literature
Created: 23 Sep 2021, 10:03 a.m.

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

Phenotypes
Intellectual disability; Dysmorphic features; Microcephaly; Seizures; Hypotonia

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Intellectual disability
  • Dysmorphic features
  • Microcephaly
  • Seizures
  • Hypotonia
Tags
Q3_21_rating
OMIM
603002
Clinvar variants
Variants in TNPO2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

23 Sep 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: tnpo2 has been classified as Amber List (Moderate Evidence).

23 Sep 2021, Gel status: 1

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

Arina Puzriakova (Genomics England Curator)

gene: TNPO2 was added gene: TNPO2 was added to Severe microcephaly. Sources: Literature Q3_21_rating tags were added to gene: TNPO2. Mode of inheritance for gene: TNPO2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TNPO2 were set to 34314705 Phenotypes for gene: TNPO2 were set to Intellectual disability; Dysmorphic features; Microcephaly; Seizures; Hypotonia Review for gene: TNPO2 was set to GREEN