Human Gene Module / Chromosome 2 / CTNNA2

CTNNA2catenin alpha 2

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
3 / 5
Rare Variants / Common Variants
10 / 0
Aliases
CTNNA2, CAP-R,  CAPR,  CT114,  CTNR
Associated Syndromes
-
Chromosome Band
2p12
Associated Disorders
-
Relevance to Autism

Biallelic variants in the CTNNA2 gene were identified in seven individuals from three consanguineous families presenting with a syndrome characterized by neuronal migration defects and pachygyria, global developmental delay (including delayed or absent social development), intellectual disability, seizures, and autistic features (Schaffer et al., 2018).

Molecular Function

May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system. Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development.

External Links
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Human
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SFARI Genomic Platforms
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Reports related to CTNNA2 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Biallelic loss of human CTNNA2, encoding ?N-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration Schaffer AE , et al. (2018) No Pachygyria
2 Support - Tuncay IO et al. (2022) Yes -
3 Recent Recommendation - Kim IB et al. (2022) Yes -
4 Support - N.Y.) (07/2) No -
5 Support - Zhou X et al. (2022) Yes -
Rare Variants   (10)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1536C>T p.Val512%3D synonymous_variant De novo - - 35901164 N.Y.) (07/2)
c.2509C>T p.Arg837Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.1652T>C p.Ile551Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.-135+54906G>A - intron_variant De novo - Simplex 35840799 Kim IB et al. (2022)
c.2002G>A p.Ala668Thr missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1057-136975C>T - intron_variant Familial Both parents Simplex 35190550 Tuncay IO et al. (2022)
c.1057-137036C>T - intron_variant Familial Both parents Simplex 35190550 Tuncay IO et al. (2022)
c.1480C>T p.Arg494Ter stop_gained Familial Both parents Simplex 30013181 Schaffer AE , et al. (2018)
c.2341C>T p.Arg781Ter stop_gained Familial Both parents Multiplex 30013181 Schaffer AE , et al. (2018)
c.2664C>T p.Thr888= stop_gained Familial Both parents Extended multiplex 30013181 Schaffer AE , et al. (2018)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Biallelic variants in the CTNNA2 gene were identified in seven individuals from three consanguineous families presenting with a syndrome characterized by neuronal migration defects and pachygyria, global developmental delay (including delayed or absent social development), intellectual disability, seizures, and autistic features (Schaffer et al., 2018).

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
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."

10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Biallelic variants in the CTNNA2 gene were identified in seven individuals from three consanguineous families presenting with a syndrome characterized by neuronal migration defects and pachygyria, global developmental delay (including delayed or absent social development), intellectual disability, seizures, and autistic features (Schaffer et al., 2018).

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.57530558447619

Ranking 654/25841 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 0.99971795284731

Ranking 828/18225 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 0.95040472826091

Ranking 18479/18665 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 0.15052536543401

Ranking 5167/20870 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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