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Mackenzie's Mission_Reproductive Carrier Screening

Gene: SEC23A

Green List (high evidence)

SEC23A (Sec23 homolog A, coat complex II component)
EnsemblGeneIds (GRCh38): ENSG00000100934
EnsemblGeneIds (GRCh37): ENSG00000100934
OMIM: 610511, Gene2Phenotype
SEC23A is in 5 panels

1 review

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

I don't know

SEC23A is an essential component of coat protein complex II (COPII)-coated vesicles that transport secretory proteins from the endoplasmic reticulum (ER) to the Golgi complex. One family has been reported (PMID:16980979) with a homozygous missense variant and craniolenticulosutural dysplasia (CLSD), with some functional studies supporting pathogenicity. The same authors later reported another individual with similar phenotype with a paternally inherited heterozygous missense variant, this variant has 91 hets in gnomAD and the father was unaffected (PMID: 21039434). They suggest digenic inheritance but found no other variants in 3 candidate genes. Zebrafish models lend some support to the gene-disease association (PMID:16980979, 16980978). This is the only reference to CDG I can find: Two individuals from the same consanguineous family were found to have biallelic variants in SEC23A and MAN1B1 (PMID: 27148587). Patients presented with carbohydrate-deficient transferrin, tall stature, obesity, macrocephaly, and maloccluded teeth (CLSD individuals present with short stature). Parents were healthy carriers for both variants and an unaffected sibling with tall stature carried the heterozygous variant in SEC23A only. The MAN1B1 variant has been previously associated with CDG and short stature. Normal SEC23A levels were identified for all family members. Pro-COL1A1 secretion was increased in patients and siblings. The authors postulate that the SEC23A variants are contributing to the tall stature in the family due to increased pro-COL1A1 secretion, and that this is a digenic disease.

In summary, there is only one family reported with convincing evidence for gene-disease association, and we have downgraded this gene on other panels.
Created: 22 Jul 2020, 6:24 a.m. | Last Modified: 22 Jul 2020, 6:24 a.m.
Panel Version: 0.7

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Craniolenticulosutural dysplasia (MIM# 607812)

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Mackenzie's Mission
Phenotypes
  • Craniolenticulosutural dysplasia, 607812 (3)
OMIM
610511
Clinvar variants
Variants in SEC23A
Penetrance
None
Panels with this gene

History Filter Activity

19 Apr 2020, Gel status: 3

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

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: SEC23A was added gene: SEC23A was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: SEC23A was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SEC23A were set to Craniolenticulosutural dysplasia, 607812 (3)