CEP57

centrosomal protein 57

Basic information

Region (hg38): 11:95789964-95832693

Links

ENSG00000166037 ∙ NCBI:9702 ∙ OMIM:607951 ∙ HGNC:30794 ∙ Uniprot:Q86XR8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mosaic variegated aneuploidy syndrome 2 (Definitive), mode of inheritance: AR
• mosaic variegated aneuploidy syndrome 2 (Strong), mode of inheritance: AR
• mosaic variegated aneuploidy syndrome 2 (Moderate), mode of inheritance: AR
• mosaic variegated aneuploidy syndrome (Supportive), mode of inheritance: AD
• mosaic variegated aneuploidy syndrome 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mosaic variegated aneuploidy syndrome 2	AR	Endocrine	Individuals have been described as manifesting with hypothyroidism (among other features), and medical replacement therapy may be beneficial	Craniofacial; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Pulmonary	12116237; 18548531; 21552266; 24259107

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CEP57 gene.

• Mosaic variegated aneuploidy syndrome 2 (380 variants)
• Inborn genetic diseases (20 variants)
• not provided (14 variants)
• not specified (1 variants)
• Mosaic variegated aneuploidy syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CEP57 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			3	77	4	84
missense			212	5	2	219
nonsense	6					6
start loss			1			1
frameshift	2	1	5			8
inframe indel			5			5
splice donor/acceptor (+/-2bp)	1	1				2
splice region			15	8	2	25
non coding			2	30	2	34
Total	9	2	228	112	8

Highest pathogenic variant AF is 0.0000197

Variants in CEP57

This is a list of pathogenic ClinVar variants found in the CEP57 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-95790701-G-A		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Feb 25, 2023)
11-95790702-G-A		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Nov 24, 2015)
11-95790706-C-T		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Sep 07, 2021)
11-95790709-C-G		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Jan 01, 2021)
11-95790713-T-G		Mosaic variegated aneuploidy syndrome 2	Likely benign (May 20, 2021)
11-95790714-GTC-G		Mosaic variegated aneuploidy syndrome 2	Pathogenic (Sep 07, 2022)
11-95790716-C-G		Mosaic variegated aneuploidy syndrome 2	Likely benign (Aug 09, 2022)
11-95790718-C-T		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Feb 21, 2023)
11-95790719-T-C		Mosaic variegated aneuploidy syndrome 2	Likely benign (Jun 23, 2022)
11-95790721-C-T		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Dec 10, 2023)
11-95790723-G-A		Mosaic variegated aneuploidy syndrome 2 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 30, 2024)
11-95790724-C-T		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Mar 08, 2022)
11-95790727-C-T		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Nov 29, 2021)
11-95790729-G-C		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Oct 22, 2023)
11-95790730-G-T		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Dec 12, 2023)
11-95790731-T-G		Mosaic variegated aneuploidy syndrome 2	Likely benign (Jun 14, 2022)
11-95790733-C-T		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Feb 25, 2022)
11-95790734-T-A		Mosaic variegated aneuploidy syndrome 2	Likely benign (Sep 20, 2021)
11-95790735-C-T		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Jan 16, 2021)
11-95790737-C-G		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Aug 23, 2022)
11-95790740-G-A		Mosaic variegated aneuploidy syndrome 2	Likely benign (Jan 19, 2022)
11-95790742-C-T		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Sep 14, 2022)
11-95790745-T-TAAGAAGCAGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTCAGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAA		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Oct 03, 2022)
11-95790748-G-A		Mosaic variegated aneuploidy syndrome 2	Uncertain significance (Aug 06, 2021)
11-95790759-C-T		Mosaic variegated aneuploidy syndrome 2	Likely benign (Jan 26, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CEP57	protein_coding	protein_coding	ENST00000325542	11	42729

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0727	0.927	125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.458	277	256	1.08	0.0000129	3296
Missense in Polyphen		113	110.8	1.0198		1501
Synonymous	-0.929	102	90.7	1.12	0.00000454	888
Loss of Function	3.72	8	30.0	0.267	0.00000180	355

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000496	0.000495
Ashkenazi Jewish	0.000299	0.000298
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000969	0.0000967
Middle Eastern	0.000109	0.000109
South Asian	0.0000654	0.0000653
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Centrosomal protein which may be required for microtubule attachment to centrosomes. May act by forming ring- like structures around microtubules. Mediates nuclear translocation and mitogenic activity of the internalized growth factor FGF2, but that of FGF1. {ECO:0000269|PubMed:22321063}.
• Disease: DISEASE: Mosaic variegated aneuploidy syndrome 2 (MVA2) [MIM:614114]: A severe developmental disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor and leukemia reported in several cases. {ECO:0000269|PubMed:21552266}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.136

Intolerance Scores

• loftool: 0.653
• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.34

Haploinsufficiency Scores

• pHI: 0.533
• hipred: N
• hipred_score: 0.479
• ghis: 0.648

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.515

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cep57
• Phenotype: homeostasis/metabolism phenotype; cellular 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); limbs/digits/tail phenotype; skeleton phenotype; respiratory system phenotype; neoplasm

Gene ontology

• Biological process: obsolete protein import into nucleus, translocation;G2/M transition of mitotic cell cycle;spermatid development;fibroblast growth factor receptor signaling pathway;regulation of G2/M transition of mitotic cell cycle;microtubule anchoring;protein homooligomerization;ciliary basal body-plasma membrane docking
• Cellular component: nucleus;Golgi apparatus;centrosome;cytosol;microtubule
• Molecular function: protein binding;microtubule binding;fibroblast growth factor binding;protein homodimerization activity;gamma-tubulin binding