Severe microcephaly

Gene: SMC5

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: 26 Sep 2024, 3:20 p.m. | Last Modified: 26 Sep 2024, 3:20 p.m.

Panel Version: 6.6

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (three unrelated cases) for the association of this gene with green rating in the next GMS update.

Created: 21 Jun 2024, 6:47 p.m. | Last Modified: 21 Jun 2024, 6:47 p.m.

Panel Version: 5.10

PMID:36333305 reported four individuals from three families with a chromosome breakage disorder and biallelic SMC5 variants. Three individuals from two families were identified with the same homozygous missense variant (p.His990Asp), while the other individual had compound heterozygous variants (p.Arg372del & p.Arg425Ter). All four patients presented with markedly severe microcephaly and reduction in height.

Evidence for functional impact of the variant was limited. However, zebrafish model recapitulated the phenotype and was not rescued by the introduction of this variant, arguing for functional effect.

This gene has been associated with relevant phenotype in both OMIM (MIM #620185) and Gene2Phenotype (with 'moderate' rating on the DD panel).
Sources: Literature

Created: 21 Jun 2024, 6:46 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Atelis syndrome 2, OMIM:620185

Publications

• 36333305