CFAP251

cilia and flagella associated protein 251, the group of WD repeat domain containing

Basic information

Region (hg38): 12:121918591-122003927

Previous symbols: [ "WDR66" ]

Links

ENSG00000158023 ∙ NCBI:144406 ∙ OMIM:618146 ∙ HGNC:28506 ∙ Uniprot:Q8TBY9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• non-syndromic male infertility due to sperm motility disorder (Supportive), mode of inheritance: AR
• spermatogenic failure 33 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 33	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	30122540; 30122541

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CFAP251 gene.

• Inborn genetic diseases (19 variants)
• not provided (12 variants)
• not specified (2 variants)
• CFAP251-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CFAP251 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				4		4
missense			21	3	3	27
nonsense	1					1
start loss						0
frameshift						0
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	1	0	21	8	4

Highest pathogenic variant AF is 0.0000131

Variants in CFAP251

This is a list of pathogenic ClinVar variants found in the CFAP251 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-121921266-T-C			Benign (Apr 22, 2022)
12-121921324-G-A		not specified	Uncertain significance (Oct 10, 2023)
12-121921327-C-A		not specified	Uncertain significance (Oct 05, 2023)
12-121921351-G-A		not specified	Uncertain significance (Dec 15, 2023)
12-121921387-C-T		not specified	Uncertain significance (Oct 05, 2023)
12-121921424-CA-C		Spermatogenic failure 33 • Non-syndromic male infertility due to sperm motility disorder;Male infertility with teratozoospermia due to single gene mutation	Pathogenic (Mar 04, 2024)
12-121921475-C-T		not specified	Likely benign (Dec 01, 2022)
12-121921483-G-A		not specified	Uncertain significance (Dec 16, 2023)
12-121921490-G-A			Uncertain significance (Apr 01, 2021)
12-121921491-G-GGAGGAGGAGGAGGAGAAA			Likely benign (Apr 01, 2021)
12-121921510-G-A		not specified	Uncertain significance (Jan 23, 2024)
12-121921519-A-G		not specified	Uncertain significance (Nov 30, 2022)
12-121921526-T-C		not specified	Uncertain significance (Feb 28, 2023)
12-121921624-A-G		not specified	Uncertain significance (Feb 06, 2024)
12-121921631-G-A		not specified	Uncertain significance (Feb 14, 2023)
12-121921636-G-T		Spermatogenic failure 33 • Non-syndromic male infertility due to sperm motility disorder;Male infertility with teratozoospermia due to single gene mutation	Pathogenic (Mar 04, 2024)
12-121923694-G-C		not specified	Uncertain significance (Dec 19, 2022)
12-121923696-C-T		CFAP251-related disorder	Likely benign (Jul 10, 2019)
12-121923758-G-C		not specified	Uncertain significance (Oct 16, 2023)
12-121923805-C-T		CFAP251-related disorder	Likely benign (Nov 01, 2022)
12-121923814-C-G		not specified	Uncertain significance (Dec 27, 2023)
12-121923864-G-A		CFAP251-related disorder	Likely benign (Feb 20, 2019)
12-121923889-G-A		not specified	Likely benign (Oct 25, 2022)
12-121923947-A-G		not specified	Uncertain significance (Jun 24, 2022)
12-121923965-A-G		not specified	Uncertain significance (Jan 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CFAP251	protein_coding	protein_coding	ENST00000288912	21	86066

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.94e-13	1.00	124884	0	132	125016	0.000528

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.584	579	620	0.934	0.0000324	7540
Missense in Polyphen		97	126.84	0.76474		1570
Synonymous	0.501	232	242	0.959	0.0000145	2174
Loss of Function	3.28	30	56.7	0.529	0.00000268	716

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00194	0.00193
Ashkenazi Jewish	0.00	0.00
East Asian	0.000341	0.000330
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000630	0.000626
Middle Eastern	0.000341	0.000330
South Asian	0.000178	0.000163
Other	0.000701	0.000658

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May regulate cilium motility through its role in the assembly of the axonemal radial spokes. {ECO:0000250|UniProtKB:A8IRK7, ECO:0000250|UniProtKB:Q24DE2}.

Intolerance Scores

• loftool: 0.966
• rvis_EVS: 1.41
• rvis_percentile_EVS: 94.8

Haploinsufficiency Scores

• pHI: 0.163
• hipred: N
• hipred_score: 0.233
• ghis: 0.453

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.545

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wdr66

Zebrafish Information Network

• Gene name: wdr66
• Affected structure: thrombocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: cilium movement
• Cellular component: radial spoke stalk;axoneme;motile cilium