WDR62

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

Basic information

Region (hg38): 19:36054648-36105108

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 (667 variants)
• Microcephaly 2, primary, autosomal recessive, with or without cortical malformations (232 variants)
• not specified (124 variants)
• Inborn genetic diseases (90 variants)
• Intellectual disability (6 variants)
• Primary Microcephaly 2 With or Without Cortical Malformations (4 variants)
• Primary Microcephaly, Recessive (3 variants)
• WDR62-related condition (3 variants)
• Microcephaly, cortical malformations, and intellectual disability (3 variants)
• Autosomal recessive primary microcephaly (2 variants)
• WDR62 Related Disorder (2 variants)
• Abnormal cerebral morphology (1 variants)
• Microcephaly (1 variants)
• Primary microcephaly type 2 (1 variants)
• Abnormality of the nervous system (1 variants)
• Global developmental delay;Seizure (1 variants)
• Seizure (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.

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			19	102	9	130
missense	3	7	305	13	10	338
nonsense	13	4	1			18
start loss						0
frameshift	19	10	3			32
inframe indel			6			6
splice donor/acceptor (+/-2bp)	5	7				12
splice region	1	2	16	18	4	41
non coding			17	114	58	189
Total	40	28	351	229	77

Highest pathogenic variant AF is 0.0000788

Variants in WDR62

This is a list of pathogenic ClinVar variants found in the WDR62 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-36054937-A-G		not specified	Likely benign (Apr 14, 2017)
19-36054981-G-C		Primary Microcephaly 2 With or Without Cortical Malformations • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jul 18, 2022)
19-36054985-G-A			Uncertain significance (Jul 18, 2022)
19-36054987-T-G			Uncertain significance (Jul 03, 2022)
19-36054992-A-T			Likely benign (Aug 04, 2023)
19-36054997-A-G			Uncertain significance (Oct 11, 2021)
19-36054999-G-T			Uncertain significance (Sep 17, 2021)
19-36055003-G-C		Microcephaly 2, primary, autosomal recessive, with or without cortical malformations	Uncertain significance (Apr 03, 2013)
19-36055008-G-C			Uncertain significance (Aug 15, 2016)
19-36055011-G-T			Uncertain significance (Mar 26, 2022)
19-36055021-A-C			Uncertain significance (Jan 13, 2022)
19-36055027-C-T			Uncertain significance (Apr 01, 2022)
19-36055028-C-G			Likely benign (Sep 08, 2018)
19-36055035-A-C		Microcephaly 2, primary, autosomal recessive, with or without cortical malformations	Uncertain significance (Jan 13, 2018)
19-36055037-G-A		Microcephaly 2, primary, autosomal recessive, with or without cortical malformations	Uncertain significance (Sep 08, 2021)
19-36055040-G-A			Likely benign (Sep 17, 2022)
19-36055044-G-GT		Microcephaly 2, primary, autosomal recessive, with or without cortical malformations	Uncertain significance (Oct 26, 2018)
19-36055053-C-G		Microcephaly 2, primary, autosomal recessive, with or without cortical malformations	Uncertain significance (Nov 15, 2012)
19-36055053-C-T		Microcephaly 2, primary, autosomal recessive, with or without cortical malformations	Conflicting classifications of pathogenicity (Nov 19, 2023)
19-36055076-C-T			Likely benign (Jan 25, 2024)
19-36055080-G-C		not specified	Benign (Mar 06, 2015)
19-36055087-C-G			Uncertain significance (Apr 15, 2022)
19-36055089-A-G		Microcephaly 2, primary, autosomal recessive, with or without cortical malformations • Inborn genetic diseases	Uncertain significance (Mar 27, 2023)
19-36055092-T-A		Microcephaly 2, primary, autosomal recessive, with or without cortical malformations • Seizure	Conflicting classifications of pathogenicity (Dec 04, 2023)
19-36055107-A-C		Inborn genetic diseases	Uncertain significance (Jun 15, 2021)

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