CDCA7

Chr 2AR

cell division cycle associated 7

Also known as: ICF3, JPO1

NCBI Gene: 83879 ENSG00000144354 UniProt: Q9BWT1 OMIM: 609937

This gene was identified as a c-Myc responsive gene, and behaves as a direct c-Myc target gene. Overexpression of this gene is found to enhance the transformation of lymphoblastoid cells, and it complements a transformation-defective Myc Box II mutant, suggesting its involvement in c-Myc-mediated cell transformation. Two alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.581 OMIM phenotype

Clinical Summary— CDCA7

🧬

Gene-Disease Validity (ClinGen)

immunodeficiency-centromeric instability-facial anomalies syndrome 3 · ARModerate

Moderate evidence — consider for supplementary testing

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 118 VUS of 289 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?

0.58LOEUF

pLI 0.011

Z-score 3.12

OE 0.32 (0.19–0.58)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.59Z-score

OE missense 0.73 (0.65–0.82)

203 obs / 277.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.32 (0.19–0.58)

0≤0.351.4

Missense OE?0.73 (0.65–0.82)

0≤0.61.4

Synonymous OE?0.78

0≤1.21.6

LoF obs/exp: 8 / 24.8Missense obs/exp: 203 / 277.3Syn Z: 1.73

This gene — mechanism propensity

0.6453th %ile

GOF

0.3292th %ile

LOF

0.4529th %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

289 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic3

VUS118

Likely Benign140

Benign14

Conflicting2

Pathogenic

Likely Pathogenic

118

VUS

140

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	0	1
Likely Pathogenic	0	3	0	0	3
VUS	12	101	2	3	118
Likely Benign	0	3	63	74	140
Benign	0	0	9	5	14
Conflicting	—				2
Total	12	107	75	82	278

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap CDCA7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →