COG2

component of oligomeric golgi complex 2, the group of Components of oligomeric golgi complex

Basic information

Region (hg38): 1:230642480-230693982

Previous symbols: [ "LDLC" ]

Links

ENSG00000135775 ∙ NCBI:22796 ∙ OMIM:606974 ∙ HGNC:6546 ∙ Uniprot:Q14746 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital disorder of glycosylation, type IIq (Limited), mode of inheritance: AR
• congenital disorder of glycosylation, type IIq (Strong), mode of inheritance: AR
• congenital disorder of glycosylation, type IIq (Supportive), mode of inheritance: AR
• congenital disorder of glycosylation, type IIq (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type IIq	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Gastrointestinal; Hematologic; Neurologic	24784932
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COG2 gene.

• Congenital disorder of glycosylation, type IIq (102 variants)
• not provided (67 variants)
• Inborn genetic diseases (25 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COG2 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	34	8	44
missense			55	6	2	63
nonsense		2				2
start loss						0
frameshift	2		1			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	5		6
non coding				20	39	59
Total	2	2	58	60	49

Highest pathogenic variant AF is 0.00000658

Variants in COG2

This is a list of pathogenic ClinVar variants found in the COG2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-230642497-AC-A			Benign (May 27, 2021)
1-230642642-G-A		Congenital disorder of glycosylation, type IIq	Likely benign (Aug 04, 2023)
1-230642648-G-A		Congenital disorder of glycosylation, type IIq	Likely benign (Jul 15, 2022)
1-230642654-C-A		See cases	Likely pathogenic (Dec 18, 2020)
1-230642745-G-C			Benign (Sep 05, 2018)
1-230659431-T-C			Benign (Sep 05, 2018)
1-230659445-C-T		Congenital disorder of glycosylation, type IIq	Likely benign (Aug 23, 2022)
1-230659454-T-C			Likely benign (Apr 26, 2018)
1-230659472-C-T		Congenital disorder of glycosylation, type IIq	Uncertain significance (Jul 04, 2022)
1-230659476-G-A		not specified	Uncertain significance (Sep 22, 2023)
1-230659500-A-G		Congenital disorder of glycosylation, type IIq	Uncertain significance (Aug 23, 2022)
1-230659506-C-T		Congenital disorder of glycosylation, type IIq • not specified	Uncertain significance (Dec 28, 2022)
1-230659507-G-A		Congenital disorder of glycosylation, type IIq	Uncertain significance (Dec 18, 2020)
1-230659523-A-G			Likely benign (Jun 17, 2018)
1-230659536-C-T		Congenital disorder of glycosylation, type IIq	Likely benign (Oct 20, 2023)
1-230659542-C-T		Congenital disorder of glycosylation, type IIq	Uncertain significance (Aug 09, 2022)
1-230659565-A-G		Congenital disorder of glycosylation, type IIq	Likely benign (Apr 20, 2022)
1-230659574-C-T		Congenital disorder of glycosylation, type IIq	Benign (Jan 23, 2024)
1-230659575-G-A		Congenital disorder of glycosylation, type IIq • not specified	Uncertain significance (Nov 21, 2022)
1-230659580-C-T		Congenital disorder of glycosylation, type IIq	Likely benign (Aug 17, 2023)
1-230659609-A-G		Congenital disorder of glycosylation, type IIq • COG2-related disorder	Likely benign (Jan 24, 2024)
1-230659895-A-G			Benign (Sep 05, 2018)
1-230660494-C-T			Benign (Apr 10, 2019)
1-230660580-A-G			Benign (Sep 04, 2018)
1-230660629-A-C			Benign (Oct 16, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COG2	protein_coding	protein_coding	ENST00000366669	18	51494

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000937	1.00	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.854	351	399	0.880	0.0000214	4830
Missense in Polyphen		86	121.45	0.70808		1499
Synonymous	-1.04	168	152	1.11	0.00000886	1396
Loss of Function	3.63	16	41.1	0.389	0.00000219	501

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000342	0.000337
Ashkenazi Jewish	0.000103	0.0000992
East Asian	0.000164	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000885	0.0000879
Middle Eastern	0.000164	0.000163
South Asian	0.0000997	0.0000980
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for normal Golgi morphology and function.
• Disease: DISEASE: Congenital disorder of glycosylation 2Q (CDG2Q) [MIM:617395]: A form of congenital disorder of glycosylation, a genetically heterogeneous group of autosomal recessive, multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. The transmission pattern of CDG2Q is consistent with autosomal recessive inheritance. {ECO:0000269|PubMed:24784932}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Intra-Golgi traffic;COPI-mediated anterograde transport;ER to Golgi Anterograde Transport;Retrograde transport at the Trans-Golgi-Network;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.251

Intolerance Scores

• loftool: 0.832
• rvis_EVS: -0.33
• rvis_percentile_EVS: 30.82

Haploinsufficiency Scores

• pHI: 0.144
• hipred: N
• hipred_score: 0.434
• ghis: 0.549

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.822

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cog2
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: endoplasmic reticulum to Golgi vesicle-mediated transport;intra-Golgi vesicle-mediated transport;Golgi organization;protein transport
• Cellular component: Golgi membrane;Golgi stack;cytosol;Golgi transport complex;trans-Golgi network membrane
• Molecular function: protein binding;protein transporter activity;protein-containing complex binding