SDHAF2

succinate dehydrogenase complex assembly factor 2, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 11:61430041-61446733

Previous symbols: [ "PGL2", "C11orf79" ]

Links

ENSG00000167985 ∙ NCBI:54949 ∙ OMIM:613019 ∙ HGNC:26034 ∙ Uniprot:Q9NX18 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• paragangliomas 2 (Strong), mode of inheritance: AD
• hereditary pheochromocytoma-paraganglioma (Supportive), mode of inheritance: AD
• paragangliomas 2 (Strong), mode of inheritance: AD
• paragangliomas 2 (Definitive), mode of inheritance: AD
• hereditary pheochromocytoma-paraganglioma (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pheochromocytoma/paraganglioma syndrome 2	AD	Oncologic	The condition involves increased risk of certain types of neoplasms, and surveillance/early treatment of tumors (eg, surgical resection) may be beneficial	Oncologic	6286462; 19628817; 20071235; 21348866; 20301715; 21224366; 22584701; 23061808; 23078982

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SDHAF2 gene.

• Hereditary pheochromocytoma-paraganglioma (386 variants)
• Hereditary cancer-predisposing syndrome (261 variants)
• not provided (60 variants)
• Paragangliomas 2 (50 variants)
• not specified (16 variants)
• Pheochromocytoma (6 variants)
• Ovarian cancer (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SDHAF2 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			1	101		102
missense	1	1	226	5		233
nonsense	6	3	3			12
start loss			2			2
frameshift	6	4	7			17
inframe indel			4			4
splice donor/acceptor (+/-2bp)		7	4			11
splice region			11	12		23
non coding			16	40	13	69
Total	13	15	263	146	13

Variants in SDHAF2

This is a list of pathogenic ClinVar variants found in the SDHAF2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-61430097-G-T		not specified	Likely benign (Nov 24, 2017)
11-61430118-G-A		Hereditary pheochromocytoma-paraganglioma	Uncertain significance (Jan 13, 2018)
11-61430136-A-G		not specified • Hereditary pheochromocytoma-paraganglioma	Likely benign (Nov 29, 2022)
11-61430142-G-A		Hereditary cancer-predisposing syndrome	Uncertain significance (Oct 15, 2021)
11-61430142-G-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Apr 26, 2018)
11-61430143-G-A		Hereditary cancer-predisposing syndrome • SDHAF2-related disorder	Conflicting classifications of pathogenicity (Mar 20, 2023)
11-61430146-A-C		Hereditary cancer-predisposing syndrome • Hereditary pheochromocytoma-paraganglioma	Conflicting classifications of pathogenicity (Dec 13, 2023)
11-61430148-T-C		Hereditary pheochromocytoma-paraganglioma • Hereditary cancer-predisposing syndrome	Uncertain significance (Sep 26, 2023)
11-61430149-G-A		Hereditary pheochromocytoma-paraganglioma • Hereditary cancer-predisposing syndrome	Uncertain significance (Aug 28, 2023)
11-61430150-G-A		Hereditary pheochromocytoma-paraganglioma	Uncertain significance (Oct 04, 2023)
11-61430150-G-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Dec 19, 2022)
11-61430151-C-A		Paragangliomas 2	Uncertain significance (Jul 07, 2023)
11-61430151-C-T		Hereditary pheochromocytoma-paraganglioma • Hereditary cancer-predisposing syndrome	Uncertain significance (Nov 30, 2023)
11-61430152-G-A		Hereditary pheochromocytoma-paraganglioma • Hereditary cancer-predisposing syndrome • Paragangliomas 2 • SDHAF2-related disorder	Likely benign (Feb 05, 2024)
11-61430152-G-T		Hereditary cancer-predisposing syndrome • Hereditary pheochromocytoma-paraganglioma	Conflicting classifications of pathogenicity (Dec 12, 2023)
11-61430152-GGTGTCTACAGT-G		Paragangliomas 2 • Hereditary pheochromocytoma-paraganglioma	Likely pathogenic (Jun 26, 2023)
11-61430153-G-A		Hereditary cancer-predisposing syndrome	Uncertain significance (Jun 13, 2019)
11-61430153-G-T		Hereditary cancer-predisposing syndrome • Hereditary pheochromocytoma-paraganglioma • SDHAF2-related disorder	Conflicting classifications of pathogenicity (Feb 08, 2024)
11-61430154-T-C		Hereditary pheochromocytoma-paraganglioma • Hereditary cancer-predisposing syndrome	Uncertain significance (Jan 19, 2024)
11-61430155-G-A		Hereditary pheochromocytoma-paraganglioma • Hereditary cancer-predisposing syndrome	Likely benign (Aug 15, 2022)
11-61430155-G-C		Hereditary pheochromocytoma-paraganglioma • Hereditary cancer-predisposing syndrome	Likely benign (Oct 22, 2023)
11-61430155-G-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Dec 09, 2022)
11-61430156-T-G		Hereditary pheochromocytoma-paraganglioma	Uncertain significance (Jul 29, 2020)
11-61430157-C-G		Hereditary pheochromocytoma-paraganglioma • Hereditary cancer-predisposing syndrome • Paragangliomas 2	Uncertain significance (Sep 19, 2023)
11-61430157-C-T		Hereditary pheochromocytoma-paraganglioma	Uncertain significance (Oct 24, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SDHAF2	protein_coding	protein_coding	ENST00000301761	4	17488

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000283	0.185	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.139	92	88.3	1.04	0.00000485	1092
Missense in Polyphen		32	30.644	1.0443		412
Synonymous	-0.747	37	31.7	1.17	0.00000153	309
Loss of Function	-0.284	8	7.18	1.11	3.09e-7	92

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol. Required for flavinylation (covalent attachment of FAD) of the flavoprotein subunit SDHA of the SDH catalytic dimer. {ECO:0000255|HAMAP-Rule:MF_03057, ECO:0000269|PubMed:19628817}.
• Disease: DISEASE: Paragangliomas 2 (PGL2) [MIM:601650]: A neural crest tumor usually derived from the chromoreceptor tissue of a paraganglion. Paragangliomas can develop at various body sites, including the head, neck, thorax and abdomen. Most commonly, they are located in the head and neck region, specifically at the carotid bifurcation, the jugular foramen, the vagal nerve, and in the middle ear. {ECO:0000269|PubMed:19628817}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.107

Intolerance Scores

• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.95

Haploinsufficiency Scores

• pHI: 0.125
• hipred: Y
• hipred_score: 0.625
• ghis: 0.468

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sdhaf2

Gene ontology

• Biological process: tricarboxylic acid cycle;mitochondrial electron transport, succinate to ubiquinone;protein dephosphorylation;negative regulation of epithelial to mesenchymal transition;protein-FAD linkage;mitochondrial respiratory chain complex II assembly;negative regulation of canonical Wnt signaling pathway
• Cellular component: nucleolus;mitochondrion;mitochondrial matrix;cytosol
• Molecular function: protein binding