CDYL2

Chr 16

chromodomain Y like 2

Also known as: PCCP1

NCBI Gene: 124359 ENSG00000166446 UniProt: Q8N8U2 OMIM: 618816

The protein functions as a transcription corepressor that negatively regulates DNA-templated transcription in the nucleus. Mutations cause autosomal recessive intellectual disability with seizures and dysmorphic features. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.6), suggesting some intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq

Predicted to enable transcription corepressor activity. Predicted to be involved in negative regulation of DNA-templated transcription. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.60

Clinical Summary— CDYL2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.

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ClinVar Variants

70 VUS of 87 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.60LOEUF

pLI 0.019

Z-score 2.95

OE 0.32 (0.18–0.60)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.11Z-score

OE missense 1.02 (0.93–1.12)

305 obs / 299.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.32 (0.18–0.60)

0≤0.351.4

Missense OE?1.02 (0.93–1.12)

0≤0.61.4

Synonymous OE?1.31

0≤1.21.6

LoF obs/exp: 7 / 21.9Missense obs/exp: 305 / 299.8Syn Z: -2.80

This gene — mechanism propensity

0.6646th %ile

GOF

0.5366th %ile

LOF

0.4038th %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

87 submitted variants in ClinVar

ClinVar

Classification Summary

VUS70

Likely Benign1

Benign2

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	70	0	70
Likely Benign	1	0	1
Benign	0	2	2
Total	71	2	73

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

View in ClinVar →

41 pathogenic / likely-pathogenic (of 56) ClinVar copy-number / structural variants overlap CDYL2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →