HBG2

hemoglobin subunit gamma 2, the group of Hemoglobin subunits

Basic information

Region (hg38): 11:5253187-5505605

Links

ENSG00000196565 ∙ NCBI:3048 ∙ OMIM:142250 ∙ HGNC:4832 ∙ Uniprot:P69892 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome (Supportive), mode of inheritance: AD
• hereditary persistence of fetal hemoglobin-sickle cell disease syndrome (Supportive), mode of inheritance: AR
• hemoglobinopathy Toms River (Supportive), mode of inheritance: AD
• cyanosis, transient neonatal (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cyanosis, transient neonatal	AD	Hematologic	Though a range of severity has been described, some individuals have been reported as requiring supplemental oxygen and/or RBC transfusions	Hematologic	6158500; 6174163; 6205403; 6208955; 2483933; 8811323; 12603090; 21561349; 22935660

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HBG2 gene.

• not provided (9 variants)
• Inborn genetic diseases (3 variants)
• Cyanosis, transient neonatal (2 variants)
• not specified (1 variants)
• HEMOGLOBIN F (AUSTELL) (1 variants)
• HEMOGLOBIN F (MELBOURNE) (1 variants)
• HEMOGLOBIN F (BROOKLYN) (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HBG2 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						0
missense	2		6	4	1	13
nonsense						0
start loss						0
frameshift						0
inframe indel		1				1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	2	1	6	4	1

Variants in HBG2

This is a list of pathogenic ClinVar variants found in the HBG2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-5253282-G-A		HEMOGLOBIN F (ONODA)	other (Aug 05, 2011)
11-5253323-T-G			Uncertain significance (Feb 03, 2022)
11-5253324-T-G			Uncertain significance (Jan 06, 2022)
11-5253330-A-C		HEMOGLOBIN F (POOLE)	other (Aug 05, 2011)
11-5253344-T-G		HEMOGLOBIN F (PORT ROYAL)	other (Aug 05, 2011)
11-5253357-C-T		HEMOGLOBIN F (CARLTON)	other (Aug 05, 2011)
11-5253360-T-G		HEMOGLOBIN F (CALTECH)	other (Aug 05, 2011)
11-5253363-C-G			Uncertain significance (Apr 20, 2021)
11-5253363-C-T		not specified	Uncertain significance (Aug 17, 2022)
11-5253366-A-G		HEMOGLOBIN F (CALABRIA)	other (Aug 18, 2016)
11-5253368-T-C		HEMOGLOBIN F (MALTA)	other (Aug 05, 2011)
11-5254292-C-G		HEMOGLOBIN F (MACEDONIA II)	other (Aug 05, 2011)
11-5254303-C-T		HEMOGLOBIN F (LA GRANGE)	other (Aug 05, 2011)
11-5254324-C-T		HEMOGLOBIN F (COLUMBUS-GA)	other (Aug 05, 2011)
11-5254330-G-A		Cyanosis, transient neonatal	Pathogenic (May 18, 2021)
11-5254366-C-T		HEMOGLOBIN F (MARIETTA)	other (Aug 05, 2011)
11-5254374-T-C		HEMOGLOBIN F (KENNESTONE)	other (Aug 05, 2011)
11-5254380-A-G		HEMOGLOBIN F (WAYNESBORO) • HEMOGLOBIN F (LESVOS)	other (Aug 05, 2011)
11-5254390-C-G		HEMOGLOBIN F (MINOO)	other (Aug 18, 2016)
11-5254405-C-T		Cyanosis, transient neonatal	Pathogenic (May 12, 2011)
11-5254407-T-C		HEMOGLOBIN F (SHANGHAI)	other (Aug 05, 2011)
11-5254408-T-G		HEMOGLOBIN F (BROOKLYN)	Likely benign (Jul 02, 2021)
11-5254409-C-G		HEMOGLOBIN F (CLARKE)	other (Aug 05, 2011)
11-5254416-T-A		Cyanosis, transient neonatal	Pathogenic (Jan 01, 2008)
11-5254417-G-A		Cyanosis, transient neonatal	Pathogenic (Jan 01, 2008)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HBG2	protein_coding	protein_coding	ENST00000380259	3	392600

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.670	0.311	124730	0	1	124731	0.00000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.35	35	65.8	0.532	0.00000303	930
Missense in Polyphen		3	22.137	0.13552		348
Synonymous	0.905	21	27.0	0.778	0.00000134	280
Loss of Function	1.76	0	3.61	0.00	1.53e-7	49

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000995	0.0000995
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.
• Disease: DISEASE: Cyanosis transient neonatal (TNCY) [MIM:613977]: A disorder characterized by cyanosis in the fetus and neonate, due to a defect in the fetal hemoglobin chain which has reduced affinity for oxygen. Some patients develop anemia resulting from increased destruction of red cells containing abnormal or unstable hemoglobin. The cyanosis resolves spontaneously by 5 to 6 months of age or earlier, as the adult beta-globin chain is produced and replaces the fetal gamma-globin chain. {ECO:0000269|PubMed:19065339, ECO:0000269|PubMed:21561349, ECO:0000269|PubMed:24502349, ECO:0000269|PubMed:2470017, ECO:0000269|PubMed:2483933, ECO:0000269|PubMed:7741137}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: ATF-2 transcription factor network (Consensus)

Recessive Scores

• pRec: 0.0956

Intolerance Scores

• loftool: 0.188
• rvis_EVS: -0.01
• rvis_percentile_EVS: 52.85

Haploinsufficiency Scores

• pHI: 0.443
• hipred: N
• hipred_score: 0.238
• ghis: 0.472

Essentials

• essential_gene_CRISPR: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.101

Gene Damage Prediction

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

Gene ontology

• Biological process: blood coagulation;oxygen transport;hydrogen peroxide catabolic process;protein heterooligomerization;cellular oxidant detoxification
• Cellular component: cytosol;hemoglobin complex;haptoglobin-hemoglobin complex;blood microparticle
• Molecular function: peroxidase activity;oxygen carrier activity;protein binding;oxygen binding;heme binding;haptoglobin binding;organic acid binding;metal ion binding