CCDC27

Chr 1

coiled-coil domain containing 27

NCBI Gene: 148870 ENSG00000162592 UniProt: Q2M243

The CCDC27 protein is a coiled-coil domain-containing protein involved in centriole and centrosome function, which are critical for proper cell division and cilia formation. Mutations cause autosomal recessive intellectual disability with seizures and developmental delay. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

Research

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.43

Clinical Summary— CCDC27

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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

118 VUS of 142 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.43LOEUF

pLI 0.000

Z-score -0.56

OE 1.10 (0.85–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.06Z-score

OE missense 1.01 (0.93–1.10)

368 obs / 364.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.10 (0.85–1.43)

0≤0.351.4

Missense OE?1.01 (0.93–1.10)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 40 / 36.3Missense obs/exp: 368 / 364.7Syn Z: -0.79

This gene — mechanism propensity

0.6453th %ile

GOF

0.5562th %ile

LOF

0.4136th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

142 submitted variants in ClinVar

ClinVar

Classification Summary

VUS118

Likely Benign16

Benign1

118

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	118	0	118
Likely Benign	12	4	16
Benign	1	0	1
Total	131	4	135

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

View in ClinVar →

90 pathogenic / likely-pathogenic (of 104) ClinVar copy-number / structural variants overlap CCDC27 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →