GDF2

growth differentiation factor 2, the group of Transforming growth factor beta superfamily

Basic information

Region (hg38): 10:47322453-47327588

Links

ENSG00000263761 ∙ NCBI:2658 ∙ OMIM:605120 ∙ HGNC:4217 ∙ Uniprot:Q9UK05 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• telangiectasia, hereditary hemorrhagic, type 1 (Strong), mode of inheritance: AD
• telangiectasia, hereditary hemorrhagic, type 5 (Moderate), mode of inheritance: AD
• hereditary hemorrhagic telangiectasia (Supportive), mode of inheritance: AD
• telangiectasia, hereditary hemorrhagic, type 5 (Limited), mode of inheritance: Unknown
• telangiectasia, hereditary hemorrhagic, type 5 (Limited), mode of inheritance: AR
• telangiectasia, hereditary hemorrhagic, type 5 (Moderate), mode of inheritance: AD
• pulmonary arterial hypertension (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hereditary hemorrhagic telangiectasia, type 5	AD	Cardiovascular; Gastrointestinal; Hematologic; Obstetric; Pharmacogenomic; Pulmonary	There are a number of surveillance/preventive/treatment based measures; These include: epistaxis treatment with humidification, lubricants, hormone therapy, anti-fibrinolytic agents, ablation, surgery, etc.; GI bleeding: iron replacement, hormonal or anti-fibrinolytic medication, surgery, etc.; Pulmonary AVM: catheter occlusion, and preventive measures such as antibiotic prophylaxis; symptomatic cerebral AVMs: surgery/embolotherapy, etc; Severe hepatic AVMs: liver transplantation if medical management fails; Specific pregnancy-related screening may be indicated; Anemia: Iron replacement or transfusion; Avoidance of certain activities and use of anticoagulant and anti-inflammatory agents (including aspirin) in the case of significant bleeding; For PAH, medical therapy (eg, prostanoids, endothelin receptor antagonists, etc.) may be beneficial, but lung transplantation may be indicated	Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Pulmonary	23972370

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GDF2 gene.

• Telangiectasia, hereditary hemorrhagic, type 5 (145 variants)
• Cardiovascular phenotype (103 variants)
• not provided (25 variants)
• not specified (6 variants)
• Pulmonary arterial hypertension (3 variants)
• GDF2-related condition (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GDF2 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				110	1	111
missense		3	53	13	1	70
nonsense	1		2			3
start loss						0
frameshift	1		2			3
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding				6	5	11
Total	2	3	57	130	7

Highest pathogenic variant AF is 0.0000131

Variants in GDF2

This is a list of pathogenic ClinVar variants found in the GDF2 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-47322657-C-T			Likely benign (May 06, 2018)
10-47322678-G-A		Telangiectasia, hereditary hemorrhagic, type 5	Uncertain significance (Apr 16, 2021)
10-47322686-G-A		Telangiectasia, hereditary hemorrhagic, type 5	Likely benign (Aug 02, 2023)
10-47322699-C-CCCCTGCTGT		Telangiectasia, hereditary hemorrhagic, type 5 • GDF2-related disorder	Likely benign (Jan 25, 2024)
10-47322702-C-G		Telangiectasia, hereditary hemorrhagic, type 5	Uncertain significance (Mar 09, 2023)
10-47322702-C-T		Telangiectasia, hereditary hemorrhagic, type 5 • GDF2-related disorder • Cardiovascular phenotype	Benign/Likely benign (Jan 27, 2024)
10-47322704-G-A		Telangiectasia, hereditary hemorrhagic, type 5	Likely benign (Dec 13, 2023)
10-47322709-C-G		Telangiectasia, hereditary hemorrhagic, type 5	Uncertain significance (Apr 10, 2021)
10-47322709-C-T		Telangiectasia, hereditary hemorrhagic, type 5	Uncertain significance (Mar 01, 2023)
10-47322713-G-C		Cardiovascular phenotype	Likely benign (Sep 13, 2020)
10-47322732-G-A		Telangiectasia, hereditary hemorrhagic, type 5	Uncertain significance (Aug 27, 2023)
10-47322737-G-A		Telangiectasia, hereditary hemorrhagic, type 5	Likely benign (Sep 28, 2018)
10-47322737-G-T		Telangiectasia, hereditary hemorrhagic, type 5	Likely benign (Sep 06, 2019)
10-47322740-A-G		Cardiovascular phenotype	Likely benign (Sep 13, 2020)
10-47322741-C-T		Telangiectasia, hereditary hemorrhagic, type 5 • Cardiovascular phenotype	Benign/Likely benign (Dec 18, 2022)
10-47322744-C-T		Telangiectasia, hereditary hemorrhagic, type 5 • Pulmonary arterial hypertension	Pathogenic (Aug 10, 2023)
10-47322750-TG-T		Cardiovascular phenotype	Uncertain significance (Jun 15, 2017)
10-47322757-G-A		Telangiectasia, hereditary hemorrhagic, type 5	Uncertain significance (Aug 31, 2021)
10-47322757-G-C		Telangiectasia, hereditary hemorrhagic, type 5	Uncertain significance (Apr 24, 2022)
10-47322761-G-T		Cardiovascular phenotype	Likely benign (Oct 21, 2021)
10-47322765-G-A		Telangiectasia, hereditary hemorrhagic, type 5	Uncertain significance (Aug 01, 2023)
10-47322776-C-T		Cardiovascular phenotype • Telangiectasia, hereditary hemorrhagic, type 5	Likely benign (Jan 16, 2024)
10-47322788-A-C		Telangiectasia, hereditary hemorrhagic, type 5	Likely benign (Apr 23, 2021)
10-47322789-C-G		Telangiectasia, hereditary hemorrhagic, type 5	Uncertain significance (Nov 02, 2023)
10-47322792-G-T		Telangiectasia, hereditary hemorrhagic, type 5	Uncertain significance (May 02, 2023)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Potent circulating inhibitor of angiogenesis. Signals through the type I activin receptor ACVRL1 but not other Alks. Signaling through SMAD1 in endothelial cells requires TGF-beta coreceptor endoglin/ENG. {ECO:0000269|PubMed:18309101, ECO:0000269|PubMed:21710321, ECO:0000269|PubMed:22799562, ECO:0000269|PubMed:23300529, ECO:0000269|PubMed:25237187}.
• Disease: DISEASE: Telangiectasia, hereditary hemorrhagic, 5 (HHT5) [MIM:615506]: A multisystemic vascular dysplasia leading to dilation of permanent blood vessels and arteriovenous malformations of skin, mucosa, and viscera. The disease is characterized by recurrent epistaxis and gastro-intestinal hemorrhage. Visceral involvement includes arteriovenous malformations of the lung, liver, and brain. {ECO:0000269|PubMed:23972370}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signal Transduction;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;TGF-beta super family signaling pathway canonical;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;GPCR signaling-G alpha i;BMP2 signaling TGF-beta MV;Signaling by BMP;Signaling by TGF-beta family members;BMP signaling Dro;ALK1 signaling events (Consensus)

Recessive Scores

• pRec: 0.221

Intolerance Scores

• loftool: 0.113
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.88

Haploinsufficiency Scores

• pHI: 0.0552
• hipred: N
• hipred_score: 0.295
• ghis: 0.514

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.485

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gdf2
• Phenotype: vision/eye phenotype; skeleton phenotype; immune system phenotype; reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: gdf2
• Affected structure: caudal vein plexus
• Phenotype tag: abnormal
• Phenotype quality: immature

Gene ontology

• Biological process: ossification;angiogenesis;branching involved in blood vessel morphogenesis;vasculogenesis;osteoblast differentiation;negative regulation of endothelial cell proliferation;positive regulation of endothelial cell proliferation;cellular iron ion homeostasis;negative regulation of DNA replication;regulation of signaling receptor activity;negative regulation of endothelial cell migration;positive regulation of pathway-restricted SMAD protein phosphorylation;negative regulation of angiogenesis;negative regulation of cell growth;BMP signaling pathway;positive regulation of BMP signaling pathway;positive regulation of interleukin-8 production;activin receptor signaling pathway;regulation of apoptotic process;regulation of MAPK cascade;negative regulation of blood vessel endothelial cell migration;positive regulation of endothelial cell differentiation;positive regulation of osteoblast differentiation;positive regulation of angiogenesis;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;cell development;blood vessel morphogenesis;cartilage development;pathway-restricted SMAD protein phosphorylation;SMAD protein signal transduction;positive regulation of cartilage development;cellular response to BMP stimulus;negative regulation of DNA biosynthetic process
• Cellular component: extracellular region;extracellular space;cell;extracellular exosome
• Molecular function: cytokine activity;transforming growth factor beta receptor binding;protein binding;growth factor activity