TANC2

tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2, the group of Tetratricopeptide repeat domain containing|Ankyrin repeat domain containing

Basic information

Region (hg38): 17:62966235-63427703

Links

ENSG00000170921 ∙ NCBI:26115 ∙ OMIM:615047 ∙ HGNC:30212 ∙ Uniprot:Q9HCD6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual developmental disorder with autistic features and language delay, with or without seizures (Moderate), mode of inheritance: AD
• intellectual developmental disorder with autistic features and language delay, with or without seizures (Strong), mode of inheritance: AD
• intellectual developmental disorder with autistic features and language delay, with or without seizures (Strong), mode of inheritance: AD
• intellectual developmental disorder with autistic features and language delay, with or without seizures (Definitive), mode of inheritance: AD
• intellectual developmental disorder with autistic features and language delay, with or without seizures (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with autistic features and language delay, with or without seizures	AD	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	Craniofacial; Neurologic	23033978; 24463507; 31616000

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TANC2 gene.

• not_provided (293 variants)
• Inborn_genetic_diseases (211 variants)
• Intellectual_developmental_disorder_with_autistic_features_and_language_delay,_with_or_without_seizures (94 variants)
• TANC2-related_disorder (50 variants)
• Autism_spectrum_disorder (10 variants)
• not_specified (9 variants)
• Neurodevelopmental_disorder (6 variants)
• Intellectual_disability (5 variants)
• See_cases (5 variants)
• INTELLECTUAL_DEVELOPMENTAL_DISORDER_WITH_AUTISTIC_FEATURES_AND_LANGUAGE_DELAY_WITHOUT_SEIZURES (5 variants)
• Developmental_delay (4 variants)
• Epilepsy (2 variants)
• Schizophrenia (1 variants)
• Neurodevelopmental_delay (1 variants)
• INTELLECTUAL_DEVELOPMENTAL_DISORDER_WITH_AUTISTIC_FEATURES_AND_LANGUAGE_DELAY_WITH_SEIZURES (1 variants)
• Abnormality_of_the_musculoskeletal_system (1 variants)
• TANC2-related_neurodevelopmental_disorders (1 variants)
• Intellectual_Disability_with_multiple_congenital_anomalies (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TANC2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001394998.1. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	60	6	71
missense		1	404	50	1	456
nonsense	5	12	4			21
start loss			1			1
frameshift	7	16	4			27
splice donor/acceptor (+/-2bp)	4	7	1			12
Total	16	36	419	110	7

Highest pathogenic variant AF is 0.0000037300535

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TANC2	protein_coding	protein_coding	ENST00000424789	25	418144

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.31e-9	124628	0	15	124643	0.0000602

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.34	900	1.12e+3	0.803	0.0000648	12872
Missense in Polyphen		179	314.61	0.56895		3540
Synonymous	0.864	400	423	0.947	0.0000244	4060
Loss of Function	8.09	8	91.5	0.0874	0.00000548	1002

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000159	0.000159
Ashkenazi Jewish	0.000107	0.0000994
East Asian	0.0000560	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.0000820	0.0000796
Middle Eastern	0.0000560	0.0000556
South Asian	0.0000335	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Note=Defects in TANC2 has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea. {ECO:0000269|PubMed:28493397}.

Recessive Scores

• pRec: 0.114

Intolerance Scores

• loftool: 0.262
• rvis_EVS: -2.78
• rvis_percentile_EVS: 0.67

Haploinsufficiency Scores

• pHI: 0.590
• hipred: Y
• hipred_score: 0.662
• ghis: 0.580

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.219

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tanc2
• 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)

Gene ontology

• Biological process: in utero embryonic development
• Cellular component: glutamatergic synapse;postsynaptic density, intracellular component