WDR62

Chr 19AR

WD repeat domain 62

Also known as: C19orf14, MCPH2

NCBI Gene: 284403 ENSG00000075702 UniProt: O43379 OMIM: 613583

The WDR62 protein functions in cerebral cortical development and is localized to the nucleus. Autosomal recessive mutations cause primary microcephaly with or without cortical malformations and cognitive disability. The pathogenic mechanism involves disrupted cortical development during embryogenesis.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is proposed to play a role in cerebral cortical development. Mutations in this gene have been associated with microencephaly, cortical malformations, and cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.861 OMIM phenotype

Clinical Summary— WDR62

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Gene-Disease Validity (ClinGen)

microcephaly 2, primary, autosomal recessive, with or without cortical malformations · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

126 unique Pathogenic / Likely Pathogenic· 492 VUS of 1178 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — WDR62

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.86LOEUF

pLI 0.000

Z-score 2.53

OE 0.67 (0.53–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.67Z-score

OE missense 0.94 (0.88–0.99)

803 obs / 858.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.53–0.86)

0≤0.351.4

Missense OE?0.94 (0.88–0.99)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 47 / 69.8Missense obs/exp: 803 / 858.0Syn Z: -0.42

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveWDR62-related microcephaly, cortical malformations, and intellectual developmental disorderLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6355th %ile

GOF

0.6736th %ile

LOF

0.4431th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

1178 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic62

Likely Pathogenic64

VUS492

Likely Benign354

Benign82

Conflicting101

Pathogenic

Likely Pathogenic

492

VUS

354

Likely Benign

Benign

101

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	51	5	6	0	62
Likely Pathogenic	50	12	1	1	64
VUS	6	436	32	18	492
Likely Benign	0	17	185	152	354
Benign	0	10	61	11	82
Conflicting	—				101
Total	107	480	285	182	1,155

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

14 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap WDR62 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →