TCN2

transcobalamin 2

Basic information

Region (hg38): 22:30607002-30627271

Links

ENSG00000185339 ∙ NCBI:6948 ∙ OMIM:613441 ∙ HGNC:11653 ∙ Uniprot:P20062 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• transcobalamin II deficiency (Definitive), mode of inheritance: AR
• transcobalamin II deficiency (Strong), mode of inheritance: AR
• transcobalamin II deficiency (Supportive), mode of inheritance: AR
• transcobalamin II deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Transcobalamin II deficiency	AR	Allergy/Immunology/Infectious; Biochemical	The condition can include neurocognitive impairment, hematologic anomalies (eg, anemia, panyctopenia), susceptibility to recurrent and severe infections, and gastrointestinal sequelae, and cobalamin treatment can result in prevention and/or clinical improvement, including related to developmental parameters; Awareness of immunodeficiency may allow prompt treatment of infections	Allergy/Immunology/Infectious; Biochemical; Gastrointestinal; Hematologic; Neurologic	5096637; 4138209; 128427; 3143215; 309761; 1743216; 7849710; 19373259

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TCN2 gene.

• Transcobalamin II deficiency (452 variants)
• not provided (83 variants)
• Inborn genetic diseases (21 variants)
• not specified (5 variants)
• Pancytopenia (1 variants)
• TRANSCOBALAMIN II POLYMORPHISM (1 variants)
• TCN2-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TCN2 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			5	91	3	99
missense			179	7	10	196
nonsense	7	1				8
start loss						0
frameshift	16	4				20
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2	5				7
splice region			8	21	3	32
non coding			16	75	41	132
Total	25	10	201	173	54

Highest pathogenic variant AF is 0.0000460

Variants in TCN2

This is a list of pathogenic ClinVar variants found in the TCN2 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-30607082-C-T		Transcobalamin II deficiency	Benign/Likely benign (Apr 09, 2019)
22-30607088-C-T		Transcobalamin II deficiency	Benign/Likely benign (Jun 24, 2021)
22-30607092-G-A		Transcobalamin II deficiency	Uncertain significance (Jan 13, 2018)
22-30607117-C-T		Transcobalamin II deficiency	Benign (Jan 13, 2018)
22-30607141-G-A		Transcobalamin II deficiency	Uncertain significance (Jan 12, 2018)
22-30607151-A-C		Transcobalamin II deficiency	Uncertain significance (Jan 13, 2018)
22-30607151-A-G		Transcobalamin II deficiency	Benign (Jul 15, 2018)
22-30607179-C-G		Transcobalamin II deficiency	Uncertain significance (Jan 12, 2018)
22-30607234-T-G		Transcobalamin II deficiency	Uncertain significance (Jan 12, 2018)
22-30607265-C-T		Transcobalamin II deficiency	Uncertain significance (Jan 15, 2018)
22-30607298-A-G		Transcobalamin II deficiency	Uncertain significance (Jan 13, 2018)
22-30607326-G-A		Transcobalamin II deficiency	Uncertain significance (Jan 15, 2018)
22-30607340-C-G		Transcobalamin II deficiency	Uncertain significance (Oct 03, 2023)
22-30607341-C-T		Transcobalamin II deficiency	Uncertain significance (Jul 12, 2022)
22-30607348-C-A		Transcobalamin II deficiency	Uncertain significance (Aug 26, 2021)
22-30607349-C-T		Transcobalamin II deficiency	Likely benign (Nov 24, 2023)
22-30607350-T-C		Transcobalamin II deficiency	Uncertain significance (Sep 14, 2022)
22-30607352-C-T		Transcobalamin II deficiency	Likely benign (Aug 11, 2023)
22-30607355-C-G		Transcobalamin II deficiency	Likely benign (Dec 15, 2022)
22-30607358-C-T		Transcobalamin II deficiency	Likely benign (May 17, 2023)
22-30607361-T-A		Transcobalamin II deficiency	Likely benign (Jul 16, 2019)
22-30607362-C-G		Transcobalamin II deficiency	Uncertain significance (Nov 12, 2021)
22-30607363-T-C		Transcobalamin II deficiency	Uncertain significance (Aug 30, 2023)
22-30607364-G-A		Transcobalamin II deficiency	Likely benign (Oct 07, 2023)
22-30607368-GT-G		Transcobalamin II deficiency	Pathogenic (Nov 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TCN2	protein_coding	protein_coding	ENST00000215838	9	20441

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000105	0.940	125675	0	73	125748	0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.12	322	231	1.39	0.0000128	2760
Missense in Polyphen		95	73.17	1.2983		965
Synonymous	-4.19	149	96.6	1.54	0.00000543	873
Loss of Function	1.81	13	22.2	0.585	0.00000133	232

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000756	0.000756
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000369	0.000360
Middle Eastern	0.000163	0.000163
South Asian	0.000261	0.000261
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells. {ECO:0000269|PubMed:8443384}.
• Disease: DISEASE: Transcobalamin II deficiency (TCN2 deficiency) [MIM:275350]: Results in various forms of anemia. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Vitamin digestion and absorption - Homo sapiens (human);Vitamin B12 Metabolism;One Carbon Metabolism;Cobalamin (Cbl, vitamin B12) transport and metabolism;Metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors (Consensus)

Recessive Scores

• pRec: 0.565

Intolerance Scores

• loftool: 0.808
• rvis_EVS: 1.93
• rvis_percentile_EVS: 97.49

Haploinsufficiency Scores

• pHI: 0.211
• hipred: Y
• hipred_score: 0.542

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.411

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tcn2

Gene ontology

• Biological process: cobalt ion transport;cobalamin metabolic process;cobalamin transport
• Cellular component: extracellular region;extracellular space;endosome;lysosomal lumen
• Molecular function: protein binding;cobalamin binding;metal ion binding