NCAPD2

Chr 12AR

non-SMC condensin I complex subunit D2

Also known as: CAP-D2, CNAP1, MCPH21, hCAP-D2

NCBI Gene: 9918 ENSG00000010292 UniProt: Q15021 OMIM: 615638

NCAPD2 encodes a regulatory subunit of the condensin complex that is essential for mitotic chromosome condensation and resolution of DNA catenanes between sister chromatids during cell division. Mutations cause primary autosomal recessive microcephaly 21, reflecting the protein's critical role in neurogenesis where accurate chromosome condensation in neural stem cells affects neuron pool size and cortical development. This gene is highly constrained against loss-of-function variants, indicating its essential cellular function.

OMIM ResearchSummary from RefSeq, UniProt

Enables histone binding activity. Involved in mitotic chromosome condensation and positive regulation of chromosome condensation. Located in several cellular components, including condensed chromosome; microtubule organizing center; and nuclear lumen. Part of condensin complex. Implicated in primary autosomal recessive microcephaly 21. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.581 OMIM phenotype

Clinical Summary— NCAPD2

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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

10 unique Pathogenic / Likely Pathogenic· 229 VUS of 332 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 0.000

Z-score 4.60

OE 0.44 (0.33–0.58)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.71Z-score

OE missense 0.93 (0.87–0.99)

743 obs / 799.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.33–0.58)

0≤0.351.4

Missense OE?0.93 (0.87–0.99)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 34 / 77.8Missense obs/exp: 743 / 799.4Syn Z: 0.26

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedNCAPD2-related microcephaly with short statureLOFAR

This gene — mechanism propensity

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

0.6452th %ile

GOF

0.4578th %ile

LOF

0.3357th %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.

ClinVar Variant Classifications

332 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic8

VUS229

Likely Benign37

Benign20

Conflicting5

Pathogenic

Likely Pathogenic

229

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	0	0	2
Likely Pathogenic	8	0	0	0	8
VUS	6	219	4	0	229
Likely Benign	0	22	5	10	37
Benign	0	5	4	11	20
Conflicting	—				5
Total	16	246	13	21	301

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

View in ClinVar →

46 pathogenic / likely-pathogenic (of 58) ClinVar copy-number / structural variants overlap NCAPD2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →