NCAPD2

non-SMC condensin I complex subunit D2, the group of Armadillo like helical domain containing|Condensin I subunits

Basic information

Region (hg38): 12:6493355-6531955

Links

ENSG00000010292 ∙ NCBI:9918 ∙ OMIM:615638 ∙ HGNC:24305 ∙ Uniprot:Q15021 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly 21, primary, autosomal recessive (Moderate), mode of inheritance: AR
• microcephaly 21, primary, autosomal recessive (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly 21, primary, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	27737959; 28097321

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NCAPD2 gene.

• Inborn genetic diseases (76 variants)
• not provided (34 variants)
• Microcephaly 21, primary, autosomal recessive (14 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NCAPD2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	7	11
missense			77	6	4	87
nonsense			1			1
start loss						0
frameshift	1	2	1			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2	2	1			5
splice region			4	2	2	8
non coding					3	3
Total	3	4	81	10	14

Highest pathogenic variant AF is 0.000204

Variants in NCAPD2

This is a list of pathogenic ClinVar variants found in the NCAPD2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-6495075-G-A			Uncertain significance (May 19, 2022)
12-6495103-C-G		Inborn genetic diseases • NCAPD2-related disorder	Likely benign (May 10, 2022)
12-6495106-C-A		Inborn genetic diseases • NCAPD2-related disorder	Likely benign (May 10, 2022)
12-6495252-C-T		Microcephaly 21, primary, autosomal recessive	Benign (Sep 05, 2021)
12-6509720-T-C		Inborn genetic diseases	Uncertain significance (Dec 14, 2023)
12-6510082-C-T			Uncertain significance (Mar 12, 2022)
12-6510114-T-C		NCAPD2-related disorder	Benign (Jun 13, 2019)
12-6510118-C-G		Microcephaly 21, primary, autosomal recessive	Benign (Mar 10, 2022)
12-6510732-T-C			Benign (Dec 31, 2019)
12-6510743-G-A		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
12-6510754-T-A		Inborn genetic diseases	Uncertain significance (Jul 12, 2023)
12-6511109-G-T			Likely pathogenic (Jan 01, 2018)
12-6511229-A-C			Benign (Dec 01, 2023)
12-6514297-A-G		Inborn genetic diseases	Uncertain significance (Aug 21, 2023)
12-6514326-C-T			Uncertain significance (Sep 01, 2021)
12-6514356-C-T		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
12-6514538-C-G		Inborn genetic diseases	Uncertain significance (Aug 18, 2022)
12-6514594-C-T			Likely benign (Jul 01, 2022)
12-6514774-G-A		Inborn genetic diseases	Uncertain significance (Dec 17, 2023)
12-6514808-G-A		Inborn genetic diseases	Uncertain significance (Aug 02, 2023)
12-6514831-T-A		Inborn genetic diseases	Uncertain significance (Dec 13, 2022)
12-6516815-TTC-T		NCAPD2-related disorder	Likely benign (Dec 16, 2019)
12-6516849-G-A			Conflicting classifications of pathogenicity (Dec 31, 2019)
12-6516866-G-A		NCAPD2-related disorder	Likely benign (Dec 24, 2019)
12-6516872-G-A		Inborn genetic diseases	Uncertain significance (Aug 23, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NCAPD2	protein_coding	protein_coding	ENST00000315579	31	38600

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.08e-12	1.00	125535	0	213	125748	0.000847

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.709	743	799	0.929	0.0000462	9124
Missense in Polyphen		189	218.25	0.86599		2560
Synonymous	0.262	288	294	0.981	0.0000149	2826
Loss of Function	4.60	34	77.8	0.437	0.00000447	828

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00160	0.00160
Ashkenazi Jewish	0.00228	0.00228
East Asian	0.000326	0.000326
Finnish	0.000510	0.000508
European (Non-Finnish)	0.000960	0.000959
Middle Eastern	0.000326	0.000326
South Asian	0.000555	0.000555
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. May target the condensin complex to DNA via its C-terminal domain. {ECO:0000269|PubMed:11136719}.
• Pathway: akap95 role in mitosis and chromosome dynamics;Condensation of Prometaphase Chromosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic;Aurora B signaling (Consensus)

Recessive Scores

• pRec: 0.120

Intolerance Scores

• loftool: 0.771
• rvis_EVS: -0.05
• rvis_percentile_EVS: 48.95

Haploinsufficiency Scores

• pHI: 0.0551
• hipred: Y
• hipred_score: 0.648
• ghis: 0.609

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.526

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ncapd2

Zebrafish Information Network

• Gene name: ncapd2
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: mitotic chromosome condensation;meiotic chromosome condensation;cell division;chromosome separation
• Cellular component: nuclear chromosome;condensed chromosome, centromeric region;condensed chromosome;condensin complex;condensin core heterodimer;nuclear condensin complex;nucleus;nucleoplasm;cytoplasm;cytosol;membrane
• Molecular function: chromatin binding;protein binding;histone binding