SPEF2

sperm flagellar 2

Basic information

Region (hg38): 5:35617844-35814611

Links

ENSG00000152582 ∙ NCBI:79925 ∙ OMIM:610172 ∙ HGNC:26293 ∙ Uniprot:Q9C093 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spermatogenic failure 43 (Moderate), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• non-syndromic male infertility due to sperm motility disorder (Supportive), mode of inheritance: AR
• spermatogenic failure 43 (Strong), mode of inheritance: AR
• spermatogenic failure 43 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 43	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	Genitourinary	31048344; 31151990; 31278745

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPEF2 gene.

• Primary ciliary dyskinesia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPEF2 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				7	7	14
missense			105	14	16	135
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region	1		1	1	1	4
non coding				1	55	56
Total	0	2	105	22	78

Variants in SPEF2

This is a list of pathogenic ClinVar variants found in the SPEF2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-35618008-TC-T		Spermatogenic failure 43	Pathogenic (Jan 27, 2020)
5-35628484-T-C		Inborn genetic diseases	Uncertain significance (Mar 14, 2023)
5-35628492-G-A		Inborn genetic diseases	Uncertain significance (Nov 13, 2023)
5-35628718-A-G			Benign (May 17, 2021)
5-35641463-G-T		Inborn genetic diseases	Uncertain significance (Jan 04, 2022)
5-35641480-A-C		not specified • Spermatogenic failure 43	Benign (Jul 15, 2021)
5-35641489-G-A			Benign (May 04, 2021)
5-35641491-T-C			Likely benign (Oct 01, 2023)
5-35641517-A-G			Benign (May 05, 2021)
5-35641546-G-A		SPEF2-related disorder	Likely benign (Mar 23, 2022)
5-35641566-A-G			Benign (Jun 29, 2018)
5-35641573-A-G		Inborn genetic diseases	Uncertain significance (Mar 07, 2024)
5-35641633-C-T		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
5-35641667-G-A		Spermatogenic failure 43	Likely benign (Mar 10, 2022)
5-35641717-C-T			Benign (May 26, 2021)
5-35644234-T-G			Benign (May 15, 2021)
5-35644377-G-A		Inborn genetic diseases	Uncertain significance (Dec 26, 2023)
5-35644392-A-G		Inborn genetic diseases	Uncertain significance (Jul 19, 2023)
5-35644414-G-T		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
5-35644514-G-A		Inborn genetic diseases	Likely benign (Oct 12, 2022)
5-35644519-T-C		not specified • Spermatogenic failure 43	Benign (Jul 15, 2021)
5-35646682-A-G			Benign (Aug 01, 2024)
5-35646686-G-A		Inborn genetic diseases	Uncertain significance (Jun 29, 2023)
5-35646737-A-C		Inborn genetic diseases	Uncertain significance (Oct 29, 2021)
5-35646763-G-A		Inborn genetic diseases	Uncertain significance (Mar 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPEF2	protein_coding	protein_coding	ENST00000356031	37	196768

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.12e-25	1.00	125570	0	178	125748	0.000708

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.01	1008	922	1.09	0.0000467	12026
Missense in Polyphen		379	330.75	1.1459		4292
Synonymous	1.03	290	313	0.926	0.0000156	3286
Loss of Function	3.90	56	97.6	0.574	0.00000509	1236

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00146	0.00144
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.00167	0.00152
Finnish	0.000141	0.000139
European (Non-Finnish)	0.000699	0.000677
Middle Eastern	0.00167	0.00152
South Asian	0.000822	0.000784
Other	0.000499	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for correct axoneme development in spermatozoa. Important for normal development of the manchette and sperm head morphology. Essential for male fertility. Plays a role in localization of the intraflagellar transport protein IFT20 to the manchette, suggesting function as an adapter for dynein-mediated protein transport during spermatogenesis. Also plays a role in bone growth where it seems to be required for normal osteoblast differentiation. {ECO:0000250|UniProtKB:Q8C9J3}.

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.972
• rvis_EVS: 2.82
• rvis_percentile_EVS: 99.07

Haploinsufficiency Scores

• pHI: 0.119
• hipred: N
• hipred_score: 0.306
• ghis: 0.434

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0147

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spef2
• Phenotype: reproductive system phenotype; 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); respiratory system phenotype; immune system phenotype; skeleton 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); craniofacial phenotype; cellular phenotype

Gene ontology

• Biological process: spermatogenesis;cell differentiation
• Cellular component: Golgi apparatus