CTNNA2

catenin alpha 2, the group of Alpha catenins

Basic information

Region (hg38): 2:79185231-80648861

Links

ENSG00000066032 ∙ NCBI:1496 ∙ OMIM:114025 ∙ HGNC:2510 ∙ Uniprot:P26232 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cortical dysplasia, complex, with other brain malformations 9 (Moderate), mode of inheritance: AR
• cortical dysplasia, complex, with other brain malformations 9 (Strong), mode of inheritance: AR
• cortical dysplasia, complex, with other brain malformations 9 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cortical dysplasia, complex, with other brain malformations, 9	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	30013181

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CTNNA2 gene.

• Cortical dysplasia, complex, with other brain malformations 9 (1 variants)
• Hereditary breast ovarian cancer syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CTNNA2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				18	6	24
missense			31	1		32
nonsense			1			1
start loss						0
frameshift	1	1				2
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1					1
splice region			1	2		3
non coding			28	4	36	68
Total	2	1	61	23	42

Variants in CTNNA2

This is a list of pathogenic ClinVar variants found in the CTNNA2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-79523156-A-G			Benign (May 11, 2021)
2-79523417-C-T			Benign (May 11, 2021)
2-79523465-G-T			Benign (May 11, 2021)
2-79651538-A-G		Cortical dysplasia, complex, with other brain malformations 9	Benign (Jul 30, 2021)
2-79651546-C-T		CTNNA2-related disorder	Likely benign (Jul 19, 2024)
2-79651599-A-G			Uncertain significance (Mar 06, 2023)
2-79651796-T-A			Benign (May 11, 2021)
2-79744351-G-A			Benign (May 20, 2021)
2-79744386-G-A		Hereditary breast ovarian cancer syndrome	Pathogenic (Aug 01, 2020)
2-79744499-T-G		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
2-79744515-G-C		Inborn genetic diseases	Uncertain significance (Sep 17, 2021)
2-79744549-T-C		CTNNA2-related disorder	Likely benign (Dec 16, 2020)
2-79744573-C-T		Inborn genetic diseases	Uncertain significance (Jan 14, 2022)
2-79744574-G-A		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
2-79858055-C-T		Inborn genetic diseases	Uncertain significance (Apr 06, 2023)
2-79858074-C-T		CTNNA2-related disorder	Likely benign (Feb 27, 2019)
2-79858091-C-T			Uncertain significance (-)
2-79858092-G-A			Likely benign (Dec 01, 2021)
2-79858113-G-A		CTNNA2-related disorder	Benign (May 04, 2021)
2-79858120-C-T		Cortical dysplasia, complex, with other brain malformations 9	Uncertain significance (Sep 04, 2024)
2-79870079-C-T			Benign (May 12, 2021)
2-79870153-T-C			Benign (May 11, 2021)
2-79873899-G-A			Benign (May 11, 2021)
2-79873914-A-G			Benign (May 11, 2021)
2-79874144-A-G			Likely benign (Jan 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CTNNA2	protein_coding	protein_coding	ENST00000466387	17	1463549

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.425	0.575	125264	0	21	125285	0.0000838

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.63	306	544	0.562	0.0000329	5931
Missense in Polyphen		72	158.38	0.45461		1732
Synonymous	-0.223	221	217	1.02	0.0000144	1775
Loss of Function	4.82	10	44.8	0.223	0.00000263	496

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000159	0.000157
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000621	0.0000617
Middle Eastern	0.00	0.00
South Asian	0.000294	0.000294
Other	0.000167	0.000164

dbNSFP

Source: dbNSFP

• Function: 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. Functions in the control of startle modulation. {ECO:0000250|UniProtKB:Q61301}.
• Pathway: Gastric cancer - Homo sapiens (human);Adherens junction - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Arrhythmogenic Right Ventricular Cardiomyopathy;Ectoderm Differentiation;Endometrial cancer;Developmental Biology;CDO in myogenesis;Myogenesis;TGF_beta_Receptor (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.502
• rvis_EVS: -0.64
• rvis_percentile_EVS: 16.63

Haploinsufficiency Scores

• pHI: 0.392
• hipred: Y
• hipred_score: 0.777
• ghis: 0.580

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.275

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ctnna2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: cytoskeleton organization;axonogenesis;radial glia guided migration of Purkinje cell;dendrite morphogenesis;brain morphogenesis;positive regulation of muscle cell differentiation;regulation of synapse structural plasticity;prepulse inhibition;cell-cell adhesion;modification of postsynaptic actin cytoskeleton
• Cellular component: nucleus;cytoplasm;cytosol;adherens junction;cell-cell adherens junction;actin cytoskeleton;basolateral plasma membrane;lamellipodium;axon;hippocampal mossy fiber to CA3 synapse;parallel fiber to Purkinje cell synapse;presynaptic active zone cytoplasmic component;extrinsic component of presynaptic membrane;extrinsic component of postsynaptic membrane;postsynaptic density, intracellular component
• Molecular function: structural constituent of cytoskeleton;protein binding;identical protein binding;cadherin binding;actin filament binding