Mosaic variegated aneuploidy syndrome 2

Summary

Mosaic variegated aneuploidy syndrome 2 (MONDO:0013582) is a disease caused by CEP57 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CEP57 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 508

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mosaic variegated aneuploidy syndrome 2
Mondo ID	MONDO:0013582
OMIM	614114
DOID	DOID:0080142
NCIT	C168989
UMLS	C3279843
MedGen	481473
GARD	0015758
Is cancer (heuristic)	no

Also known as: CEP57 mosaic variegated aneuploidy syndrome · mosaic variegated aneuploidy syndrome 2 · mosaic variegated aneuploidy syndrome caused by mutation in CEP57 · Mosaic variegated aneuploidy syndrome type 2 · mosaic variegated aneuploidy syndrome type 2 · MVA2

Data availability: 508 ClinVar variants · 4 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › mosaic variegated aneuploidy syndrome › mosaic variegated aneuploidy syndrome 2

Related subtypes (6): mosaic variegated aneuploidy syndrome 1, mosaic variegated aneuploidy syndrome 3, mosaic variegated aneuploidy syndrome 4, mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition, Atelis syndrome 1, Atelis syndrome 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

508 retrieved; paginated sample, class counts are floors:

306 uncertain significance, 159 likely benign, 14 pathogenic, 13 conflicting classifications of pathogenicity, 8 benign, 5 likely pathogenic, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1030345	NM_014679.5(CEP57):c.1015C>T (p.Arg339Ter)	CEP57	Pathogenic	criteria provided, multiple submitters, no conflicts
1421218	NM_014679.5(CEP57):c.523C>T (p.Arg175Ter)	CEP57	Pathogenic	criteria provided, single submitter
2169972	NM_014679.5(CEP57):c.20_21del (p.Ser7fs)	CEP57	Pathogenic	criteria provided, single submitter
2425964	NC_000011.9:g.(?95523863)(95564420_?)del	CEP57	Pathogenic	criteria provided, single submitter
2873280	NM_014679.5(CEP57):c.312_313del (p.Tyr104_Lys105delinsTer)	CEP57	Pathogenic	criteria provided, single submitter
30690	NM_014679.5(CEP57):c.520_521del (p.Glu174fs)	CEP57	Pathogenic	no assertion criteria provided
30691	NM_014679.5(CEP57):c.915_925dup (p.Leu309fs)	CEP57	Pathogenic	criteria provided, multiple submitters, no conflicts
30692	NM_014679.5(CEP57):c.241C>T (p.Arg81Ter)	CEP57	Pathogenic	criteria provided, single submitter
3574131	NM_014679.5(CEP57):c.973C>T (p.Arg325Ter)	CEP57	Pathogenic	criteria provided, single submitter
4751150	NM_014679.5(CEP57):c.600del (p.Thr201fs)	CEP57	Pathogenic	criteria provided, single submitter
574305	NM_014679.5(CEP57):c.1117C>T (p.Gln373Ter)	CEP57	Pathogenic	criteria provided, single submitter
643769	NM_014679.5(CEP57):c.451C>T (p.Arg151Ter)	CEP57	Pathogenic	criteria provided, single submitter
936628	NM_014679.5(CEP57):c.778A>T (p.Lys260Ter)	CEP57	Pathogenic	criteria provided, single submitter
977798	NM_014679.5(CEP57):c.382+2T>C	CEP57	Pathogenic	criteria provided, single submitter
2161490	NM_014679.5(CEP57):c.46-2A>T	CEP57	Likely pathogenic	criteria provided, single submitter
2425963	NC_000011.9:g.(?95549619)(95562458_?)del	CEP57	Likely pathogenic	criteria provided, single submitter
2828215	NM_014679.5(CEP57):c.622-2A>G	CEP57	Likely pathogenic	criteria provided, single submitter
2884194	NM_014679.5(CEP57):c.699+1G>T	CEP57	Likely pathogenic	criteria provided, single submitter
638495	NM_014679.5(CEP57):c.1402del (p.Lys467_Leu468insTer)	CEP57	Likely pathogenic	criteria provided, single submitter
1005140	NM_014679.5(CEP57):c.1484G>A (p.Ser495Asn)	CEP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191025	NM_014679.5(CEP57):c.89G>C (p.Arg30Pro)	CEP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2073437	NM_014679.5(CEP57):c.983A>G (p.Asn328Ser)	CEP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2139874	NM_014679.5(CEP57):c.1128T>C (p.Phe376=)	CEP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3666790	NM_014679.5(CEP57):c.1061A>G (p.Asn354Ser)	CEP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
472259	NM_014679.5(CEP57):c.677G>A (p.Arg226His)	CEP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
472260	NM_014679.5(CEP57):c.751C>T (p.Pro251Ser)	CEP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
539588	NM_014679.5(CEP57):c.95C>T (p.Ser32Phe)	CEP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
575506	NM_014679.5(CEP57):c.1273C>T (p.Leu425=)	CEP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
696640	NM_014679.5(CEP57):c.764A>G (p.Asn255Ser)	CEP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
836256	NM_014679.5(CEP57):c.39C>G (p.His13Gln)	CEP57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CEP57	Definitive	Autosomal recessive	mosaic variegated aneuploidy syndrome 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CEP57	Orphanet:1052	Mosaic variegated aneuploidy syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CEP57	HGNC:30794	ENSG00000166037	Q86XR8	Centrosomal protein of 57 kDa	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CEP57	Centrosomal protein of 57 kDa	Centrosomal protein which may be required for microtubule attachment to centrosomes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CEP57	Other/Unknown	no		Cep57_MT-bd_dom, Cep57_CLD, Centrosomal_MT-associated

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
oocyte	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CEP57	292	ubiquitous	marker	oocyte, sperm, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEP57	1,345

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CEP57	Q86XR8	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Centrosome maturation	1	253.8×	0.013	CEP57
Loss of Nlp from mitotic centrosomes	1	158.6×	0.013	CEP57
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.013	CEP57
AURKA Activation by TPX2	1	152.3×	0.013	CEP57
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.013	CEP57
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.013	CEP57
Mitotic G2-G2/M phases	1	126.9×	0.013	CEP57
G2/M Transition	1	126.9×	0.013	CEP57
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.013	CEP57
Anchoring of the basal body to the plasma membrane	1	113.1×	0.013	CEP57
Cilium Assembly	1	108.8×	0.013	CEP57
Mitotic Prometaphase	1	69.2×	0.017	CEP57
Organelle biogenesis and maintenance	1	66.0×	0.017	CEP57
M Phase	1	66.0×	0.017	CEP57
Cell Cycle, Mitotic	1	48.2×	0.022	CEP57
Cell Cycle	1	36.0×	0.028	CEP57

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
fibroblast growth factor receptor signaling pathway	1	285.6×	0.008	CEP57
spermatid development	1	145.3×	0.008	CEP57
protein homooligomerization	1	122.1×	0.008	CEP57

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CEP57	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CEP57

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CEP57	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.