Human Gene Module / Chromosome 10 / CELF2

CELF2CUGBP Elav-like family member 2

SFARI Gene Score
2S
Strong Candidate, Syndromic Criteria 2.1, Syndromic
Autism Reports / Total Reports
4 / 5
Rare Variants / Common Variants
8 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
10p14
Associated Disorders
-
Relevance to Autism

A de novo frameshift variant in the CELF2 gene was identified in an ASD proband from the Autism Simplex Collection in Yuen et al., 2017. Itai et al., 2021 characterized five unrelated individuals with heterozygous CELF2 variants presenting with developmental and epileptic encephalopathy; autistic features were reported in four of five individuals in this report, and variants identified in patients with developmental and epileptic encephlopathy in this report were experimentally shown to cause aberrant CELF2 cellular localization in transfected cells. Whole-genome sequencing of prefrontal cortex from 59 donors with autism spectrum disorder (ASD) and 15 control donors in Rodin et al., 2021 identified an additional germline loss-of-function variant in CELF2 in brain tissue from a 67-year-old African American male with ASD from the University of Maryland brain bank.

Molecular Function

Members of the CELF/BRUNOL protein family contain two N-terminal RNA recognition motif (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 aa between the second and third RRM domains. Members of this protein family regulate pre-mRNA alternative splicing and may also be involved in mRNA editing, and translation.

External Links
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SFARI Genomic Platforms
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Reports related to CELF2 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
2 Recent Recommendation - Itai T et al. (2021) No Autistic features
3 Support - Rodin RE et al. (2021) Yes Epilepsy/seizures
4 Support - Zhou X et al. (2022) Yes -
5 Support - Xinyu Duan et al. () Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.272-1G>C - splice_site_variant De novo - - 33131106 Itai T et al. (2021)
c.700C>T p.Gln234Ter stop_gained De novo - - 33432195 Rodin RE et al. (2021)
c.1558C>T p.Pro520Ser missense_variant De novo - - 33131106 Itai T et al. (2021)
c.1271T>C p.Met424Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1516C>G p.Arg506Gly missense_variant Familial Maternal - 33131106 Itai T et al. (2021)
c.1562dup p.Met522HisfsTer77 frameshift_variant De novo - - 33131106 Itai T et al. (2021)
c.486_487del p.Asn163CysfsTer24 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.327dup p.Leu110IlefsTer11 frameshift_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
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
2S

Increased from to 2S

Krishnan Probability Score

Score 0.5642058063419

Ranking 1278/25841 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 0.99878580147353

Ranking 1114/18225 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 0.86145802748973

Ranking 3910/18665 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
Zhang D Score

Score 0.62452109799458

Ranking 44/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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