POMGNT2

protein O-linked mannose N-acetylglucosaminyltransferase 2 (beta 1,4-), the group of O-linked N-acetylglucosaminyltransferases

Basic information

Region (hg38): 3:43079228-43106085

Previous symbols: [ "C3orf39", "GTDC2" ]

Links

ENSG00000144647 ∙ NCBI:84892 ∙ OMIM:614828 ∙ HGNC:25902 ∙ Uniprot:Q8NAT1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 (Strong), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 (Moderate), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy, type A (Supportive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 (Definitive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 (Strong), mode of inheritance: AR
• myopathy caused by variation in POMGNT2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8	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	Musculoskeletal; Neurologic; Ophthalmologic	22958903; 27066570

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POMGNT2 gene.

• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 (378 variants)
• not provided (85 variants)
• not specified (37 variants)
• Inborn genetic diseases (32 variants)
• Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8 (5 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8;Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8 (2 variants)
• Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 (1 variants)
• POMGNT2-related condition (1 variants)
• Neonatal death;Severe hydrocephalus (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POMGNT2 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			2	118	4	124
missense	1	1	226	7		235
nonsense	4	3				7
start loss						0
frameshift	9	2	2			13
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				3	9	12
Total	14	6	232	128	13

Highest pathogenic variant AF is 0.0000197

Variants in POMGNT2

This is a list of pathogenic ClinVar variants found in the POMGNT2 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-43079537-C-A			Benign (Jun 26, 2018)
3-43079574-G-T			Benign (Apr 03, 2019)
3-43079687-C-T		not specified	Benign (Jul 05, 2016)
3-43079692-C-T		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Likely benign (Nov 25, 2020)
3-43079693-G-A		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 • Inborn genetic diseases	Uncertain significance (Dec 08, 2023)
3-43079703-C-A		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Uncertain significance (Aug 14, 2022)
3-43079707-C-T		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Likely benign (Dec 13, 2023)
3-43079714-G-GCA		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Uncertain significance (Jul 26, 2022)
3-43079716-A-C		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Uncertain significance (Jun 20, 2022)
3-43079720-G-A		Inborn genetic diseases	Uncertain significance (Feb 13, 2024)
3-43079725-CAGG-C		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Uncertain significance (Mar 18, 2022)
3-43079727-G-A		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Likely benign (Jul 12, 2023)
3-43079735-T-C		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Uncertain significance (Feb 20, 2022)
3-43079745-T-C		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Uncertain significance (Aug 27, 2021)
3-43079750-C-T		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Uncertain significance (Aug 09, 2022)
3-43079751-G-A		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 • Inborn genetic diseases • Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8	Uncertain significance (Mar 26, 2024)
3-43079763-G-A		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Likely benign (Oct 14, 2023)
3-43079772-T-C		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Uncertain significance (Nov 01, 2022)
3-43079779-C-T		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Likely benign (Dec 08, 2019)
3-43079789-T-C		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Uncertain significance (Mar 13, 2022)
3-43079802-G-C		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Uncertain significance (Feb 24, 2022)
3-43079811-G-A		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Likely benign (Nov 01, 2022)
3-43079829-C-T		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Uncertain significance (Sep 13, 2022)
3-43079830-G-A		not specified • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Likely benign (Jan 15, 2024)
3-43079839-C-T		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Likely benign (Aug 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POMGNT2	protein_coding	protein_coding	ENST00000344697	1	26845

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000556	0.884	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.955	323	375	0.861	0.0000253	3755
Missense in Polyphen		130	159.25	0.81633		1738
Synonymous	-0.387	169	163	1.04	0.0000106	1265
Loss of Function	1.53	11	18.0	0.610	0.00000104	165

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000187	0.000185
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: O-linked mannose beta-1,4-N- acetylglucosaminyltransferase that transfers UDP-N-acetyl-D- glucosamine to the 4-position of the mannose to generate N-acetyl- D-glucosamine-beta-1,4-O-D-mannosylprotein. Involved in the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N- acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate- 6-)mannose), a carbohydrate structure present in alpha- dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity. {ECO:0000269|PubMed:23929950}.
• Pathway: Mannose type O-glycan biosynthesis - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;O-linked glycosylation (Consensus)

Intolerance Scores

• rvis_EVS: -0.88
• rvis_percentile_EVS: 10.54

Haploinsufficiency Scores

• pHI: 0.218
• hipred: N
• hipred_score: 0.304
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pomgnt2
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular 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); 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)

Zebrafish Information Network

• Gene name: pomgnt2
• Affected structure: muscle
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: neuron migration;protein O-linked glycosylation;protein O-linked mannosylation
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane
• Molecular function: protein binding;acetylglucosaminyltransferase activity;protein O-GlcNAc transferase activity