Intellectual disability
Gene: AGO1
Multiple individuals reported with de novo variants in this gene, most as part of large ID cohorts so phenotypic information is scarce; however, given large number we have rated as Green.Created: 10 Apr 2021, 8:36 a.m. | Last Modified: 10 Apr 2021, 8:36 a.m.
Panel Version: 3.1003
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Intellectual disability; autism
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Changed rating of gene from Red to Amber based on current information in the literature and external expert review. There is not enough evidence to support gene-disease association rating of this gene to Green.Created: 20 Feb 2019, 5:13 p.m.
Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the ID panelCreated: 20 Feb 2019, 5:11 p.m.
Comment on publications: Added publications suggested from external expert review to support upgrading of the gene. Also added PMID: 29726122 (2018) that reports a novel 2.3 Mb, de novo, 1p34.3p34.2 deletion in a patient with who has a history of global developmental delay, mild intellectual disability, delayed bone age, bilateral vesicoureteral reflux, vocal cord paralysis, right aberrant subclavian artery, kyphoscoliosis, bilateral metatarsus adductus, and valgus knee deformity. This adds to the evolving genetic literature that haploinsufficiency of this region and genes other than AGO1, AGO3, GRIK3, SLC2A1, and RIMS3 may lead to the neurocognitive delaysCreated: 20 Feb 2019, 5:10 p.m.
AGO1 previous HGNC gene symbol was EIF2C1.Created: 20 Feb 2019, 4:59 p.m.
Comment on mode of inheritance: changed MOI- agreed with external reviewer that x linked is not appropriate for this gene and was an error.Created: 20 Feb 2019, 4:52 p.m.
PMID: 30213762 reports on an individual with a de novo missense variant in AGO1 [(NM_012199.2):c.595G>A p.(Gly199Ser)]. Hypotonia, intellectual disability, seizures and dysmorphic features were part of the phenotype. The same variant had previously been reported in a study by Hamdan et al. (2014) which has been cited among others by the authors.
Other de novo variants in AGO1 (EIF2C1) reported in the context of larger ID/ASD cohorts - most of these articles cited in the aforementioned case report.
PMID: 22495306 (Sanders et al, 2012) - p.(Thr355Ile) - ASD
PMID: 23020937 (Rauch et al, 2012) - p.(Leu190Pro) - Intellectual disability
PMID: 25363768 (Iossifov et al, 2014) - p.(Thr355Ile) - ASD
PMID: 25356899 (Hamdan et al, 2014) - p.(Gly199Ser) - Intellectual disability
PMID: 27620904 (Martinez et al, 2017) - p.(Gly195Lys) - Intellectual disability
PMID: 29346770 (Takata et al, 2018) - p.Gly199Val - ASD (Same residue as in 30213762 and 25356899)
In Decipher, 2 individuals from the DDD study with de novo missense SNVs (at least one of whom published in PMID: 28135719 - https://decipher.sanger.ac.uk/search?q=gene%3AAGO1#research-variants/results ).
The authors in 30213762 cite a previous publication with 1p34.3 microdeletions in individuals with intellectual disability, although the minimal region of overlap (289 kb in size) encompassed also AGO3 and other genes apart from AGO1.
This gene has been included either as AGO1 or as EIF2C1 in ID/ASD gene panels from different diagnostic labs.
As a result this gene can be considered for upgrade to amber or green.
NB. The gene is located in 1p34.3 and as a result the X-Linked inheritance mode registered in this panel does not apply (most probably due to a typo error in the supplement of PMID 26350204 where EIF2C1 is listed as an X-Linked gene).Created: 12 Oct 2018, 11:58 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Generalized hypotonia; Global developmental delay; Intellectual disability; Autism
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Candidate gene variant found in one ID proband. No association reported in OMIM nor G2PCreated: 31 Oct 2017, 9:57 a.m.
Mode of inheritance
Unknown
Publications
Gene: ago1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: AGO1 were changed from to Generalized hypotonia; Global developmental delay; Intellectual disability; Autism
Publications for gene: AGO1 were set to 26350204
Mode of inheritance for gene: AGO1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.
Model of inheritance for gene AGO1 was set to Unknown Publications for gene AGO1 was set to ['26350204']
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
AGO1 was added to Intellectual disabilitypanel. Sources: Expert Review Red
AGO1 was created by ellenmcdonagh