WDR62

WD repeat domain 62, the group of WD repeat domain containing

Basic information

Region (hg38): 19:36054649-36105108

Previous symbols: [ "C19orf14", "MCPH2" ]

Links

ENSG00000075702 ∙ NCBI:284403 ∙ OMIM:613583 ∙ HGNC:24502 ∙ Uniprot:O43379 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly 2, primary, autosomal recessive, with or without cortical malformations (Definitive), mode of inheritance: AR
• microcephaly 2, primary, autosomal recessive, with or without cortical malformations (Strong), mode of inheritance: AR
• microcephaly 2, primary, autosomal recessive, with or without cortical malformations (Definitive), mode of inheritance: AR
• microcephaly 2, primary, autosomal recessive, with or without cortical malformations (Strong), mode of inheritance: AR
• autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR
• microcephaly 2, primary, autosomal recessive, with or without cortical malformations (Strong), mode of inheritance: AR
• microcephaly 2, primary, autosomal recessive, with or without cortical malformations (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly 2, primary, autosomal recessive, with or without cortical malformations	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	Neurologic	10573015; 20729831; 20890279; 20890278; 21496009; 21834044; 21961505; 22308068; 23065275

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WDR62 gene.

• not_provided (712 variants)
• Microcephaly_2,_primary,_autosomal_recessive,_with_or_without_cortical_malformations (246 variants)
• Inborn_genetic_diseases (239 variants)
• not_specified (110 variants)
• WDR62-related_disorder (50 variants)
• Intellectual_disability (6 variants)
• Skraban-Deardorff_syndrome (5 variants)
• Primary_Microcephaly_2_With_or_Without_Cortical_Malformations (4 variants)
• Autosomal_recessive_primary_microcephaly (3 variants)
• Abnormal_cerebral_morphology (2 variants)
• Microcephaly,_cortical_malformations,_and_intellectual_disability (2 variants)
• Primary_Microcephaly,_Recessive (2 variants)
• Microcephaly (1 variants)
• Abnormality_of_the_nervous_system (1 variants)
• Primary_microcephaly_type_2 (1 variants)
• Abnormality_of_neuronal_migration (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WDR62 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001083961.2. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			18	178	4	200
missense	6	19	401	53	5	484
nonsense	16	9	1			26
start loss						0
frameshift	31	18	2			51
splice donor/acceptor (+/-2bp)	5	16	2			23
Total	58	62	424	231	9

Highest pathogenic variant AF is 0.00011971695

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WDR62	protein_coding	protein_coding	ENST00000401500	32	50226

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.36e-23	0.892	125629	0	119	125748	0.000473

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.667	803	858	0.936	0.0000548	9851
Missense in Polyphen		234	299.97	0.78007		3607
Synonymous	-0.419	379	369	1.03	0.0000250	3087
Loss of Function	2.53	47	69.8	0.673	0.00000351	812

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00149	0.00148
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000339	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000401	0.000396
Middle Eastern	0.000339	0.000326
South Asian	0.000558	0.000555
Other	0.00101	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for cerebral cortical development. Plays a role in neuronal proliferation and migration (PubMed:20890278, PubMed:20729831). Plays a role in mother-centriole-dependent centriole duplication; the function seems also to involve CEP152, CDK5RAP2 and CEP63 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication (PubMed:26297806). {ECO:0000269|PubMed:20729831, ECO:0000269|PubMed:20890278, ECO:0000269|PubMed:26297806}.

Intolerance Scores

• loftool: 0.892
• rvis_EVS: 0.58
• rvis_percentile_EVS: 82.18

Haploinsufficiency Scores

• pHI: 0.441
• hipred: N
• hipred_score: 0.375
• ghis: 0.480

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.819

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wdr62
• Phenotype: respiratory system phenotype; liver/biliary system phenotype; reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system 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); cellular phenotype; immune system phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: wdr62
• Affected structure: retina
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: mitotic spindle organization;centriole replication;cerebral cortex development;neurogenesis
• Cellular component: spindle pole;nucleus;centrosome;centriole;microtubule organizing center;cytosol
• Molecular function: protein binding