Severe microcephaly

Gene: TRAPPC10

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 10 Oct 2023, 2:56 p.m. | Last Modified: 10 Oct 2023, 2:56 p.m.

Panel Version: 4.33

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for associating this gene with severe microcephaly (two unrelated cases and supporting functional evidence) and hence can be promoted to GREEN at the next major review.

Created: 11 Apr 2023, 7:52 p.m. | Last Modified: 11 Apr 2023, 7:52 p.m.

Panel Version: 4.7

Biallelic variants in TRAPPC10 have been identified in two unrelated consanguineous Pakistani families that have been reported with severe microcephalic neurodevelopmental disorder. In addition, neuroanatomical brain defects and microcephaly (paralleling findings seen in the human patients) were seen in Trappc9-/- mouse model.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620027) and Gene2Phenotype (with 'limited' rating).

Created: 11 Apr 2023, 7:47 p.m. | Last Modified: 11 Apr 2023, 7:50 p.m.

Panel Version: 4.6

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with microcephaly, short stature, and speech delay, OMIM:620027

Publications

• 30167849
• 35298461

Comment on list classification: New gene added by Aleš Maver (Clinical Institute of Medical Genetics). This gene is not associated with a phenotype in OMIM, but is possibly associated with a disease in Gene2Phenotype. The affected individuals in PMID:30167849 (2 individuals from the same family) had severe ID. As I do not have access to the ESHG2021 talk, this gene has been given a Red rating until further evidence is available.

Created: 13 Sep 2021, 3:31 p.m. | Last Modified: 13 Sep 2021, 3:31 p.m.

Panel Version: 2.223

Red List (low evidence)

The study on biallelic TRAPPC10 variants in microcephaly has now been published in PMID: 35298461, reporting 8 individuals with a homozygous loss-of function variant in one family and two affected individuals from the second, unrelated family.

Created: 22 Mar 2023, 6:25 p.m. | Last Modified: 22 Mar 2023, 6:25 p.m.

Panel Version: 4.1

This gene was originally reported in association with microcephalic NDD in PMID:30167849 (biallelic missense variant) and was replicated in a large family consanguineous family with a biallelic frameshift variant - reported at the ESHG2021 conference, talk C16.4 by Rawlins).
Sources: Other

Created: 30 Aug 2021, 9:01 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microcephaly, short stature, developmental delay

Publications

• PMID: 30167849
• PMID: 35298461