Human Gene Module / Chromosome 8 / AGO2

AGO2argonaute RISC catalytic component 2

SFARI Gene Score
2S
Strong Candidate, Syndromic Criteria 2.1, Syndromic
Autism Reports / Total Reports
1 / 2
Rare Variants / Common Variants
18 / 0
Aliases
AGO2, CASC7,  EIF2C2,  LINC00980,  PPD,  Q10
Associated Syndromes
-
Chromosome Band
8q24.3
Associated Disorders
ASD
Relevance to Autism

Lessel et al., 2020 identified 13 heterozygous variants in the AGO2 gene that impaired shRNA-meidated silencing in 21 patients affected by disturbances in neurological development; all 21 affected individuals presented with intellectual disability, motor delay, and delayed speech and language development, while 9/16 (56%) of affected individuals also presented with autistic features.

Molecular Function

This gene encodes a member of the Argonaute family of proteins which play a role in RNA interference. The encoded protein is highly basic, and contains a PAZ domain and a PIWI domain. It may interact with dicer1 and play a role in short-interfering-RNA-mediated gene silencing.

External Links
Open Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to AGO2 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Germline AGO2 mutations impair RNA interference and human neurological development Lessel D et al. (2020) No Autistic features
2 Support - Zhou X et al. (2022) Yes -
Rare Variants   (18)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 33199684 Lessel D et al. (2020)
c.575T>C p.Leu192Pro missense_variant De novo - - 33199684 Lessel D et al. (2020)
c.602G>T p.Gly201Val missense_variant De novo - - 33199684 Lessel D et al. (2020)
c.1070C>T p.Thr357Met missense_variant De novo - - 33199684 Lessel D et al. (2020)
c.1717G>A p.Gly573Ser missense_variant De novo - - 33199684 Lessel D et al. (2020)
c.2252G>A p.Cys751Tyr missense_variant De novo - - 33199684 Lessel D et al. (2020)
c.608A>G p.His203Arg missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.575T>C p.Leu192Pro missense_variant De novo - Simplex 33199684 Lessel D et al. (2020)
c.601G>T p.Gly201Cys missense_variant De novo - Simplex 33199684 Lessel D et al. (2020)
c.602G>T p.Gly201Val missense_variant De novo - Simplex 33199684 Lessel D et al. (2020)
c.609T>A p.His203Gln missense_variant De novo - Simplex 33199684 Lessel D et al. (2020)
c.1091T>C p.Met364Thr missense_variant De novo - Simplex 33199684 Lessel D et al. (2020)
c.1099G>C p.Ala367Pro missense_variant De novo - Simplex 33199684 Lessel D et al. (2020)
c.2197G>C p.Gly733Arg missense_variant De novo - Simplex 33199684 Lessel D et al. (2020)
c.2280C>G p.Ser760Arg missense_variant De novo - Simplex 33199684 Lessel D et al. (2020)
c.544_546del p.Phe182del inframe_deletion De novo - Simplex 33199684 Lessel D et al. (2020)
c.1070C>T p.Thr357Met missense_variant Familial Maternal Simplex 33199684 Lessel D et al. (2020)
c.2252G>A p.Cys751Tyr missense_variant De novo - Multiplex (monozygotic twins) 33199684 Lessel D et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
2S

Strong Candidate, Syndromic

Score Delta: Score remained at 2S

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2022
icon
2

Increased from to 2

Krishnan Probability Score

Score 0.49669115733669

Ranking 2540/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.99999224896231

Ranking 430/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.94430394959564

Ranking 16023/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
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