ADAMTS2

ADAM metallopeptidase with thrombospondin type 1 motif 2, the group of ADAM metallopeptidases with thrombospondin type 1 motif

Basic information

Region (hg38): 5:179110853-179345461

Links

ENSG00000087116NCBI:9509OMIM:604539HGNC:218Uniprot:O95450AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Ehlers-Danlos syndrome, dermatosparaxis type (Definitive), mode of inheritance: AR
  • Ehlers-Danlos syndrome, dermatosparaxis type (Strong), mode of inheritance: AR
  • Ehlers-Danlos syndrome, dermatosparaxis type (Strong), mode of inheritance: AR
  • Ehlers-Danlos syndrome, dermatosparaxis type (Strong), mode of inheritance: AR
  • Ehlers-Danlos syndrome, dermatosparaxis type (Supportive), mode of inheritance: AR
  • Ehlers-Danlos syndrome, dermatosparaxis type (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Ehlers-Danlos syndrome, dermatosparaxis typeARObstetricIndividuals may be prone to injuries (especially during delivery, as multiple congenital skull fractures and intracranial hemorrhage have been reported), and knowledge may allow delivery-based interventions to decrease related morbidity and mortalityCraniofacial; Dermatologic; Musculoskeletal; Obstetric1303238; 8215497; 7735500; 10417273; 15373769; 15389701; 18973246

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADAMTS2 gene.

  • Ehlers-Danlos_syndrome,_dermatosparaxis_type (1591 variants)
  • not_provided (323 variants)
  • Inborn_genetic_diseases (171 variants)
  • not_specified (129 variants)
  • Ehlers-Danlos_syndrome (71 variants)
  • ADAMTS2-related_disorder (41 variants)
  • See_cases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADAMTS2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014244.5. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
27
clinvar
645
clinvar
7
clinvar
679
missense
2
clinvar
514
clinvar
31
clinvar
3
clinvar
550
nonsense
19
clinvar
12
clinvar
2
clinvar
33
start loss
2
2
frameshift
31
clinvar
35
clinvar
4
clinvar
70
splice donor/acceptor (+/-2bp)
16
clinvar
2
clinvar
18
Total 50 67 547 676 12

Highest pathogenic variant AF is 0.00007825902

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ADAMTS2protein_codingprotein_codingENST00000251582 22234580
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9660.03391256650831257480.000330
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.436377470.8530.00005187846
Missense in Polyphen212326.20.649913393
Synonymous-0.3903203111.030.00002332391
Loss of Function5.591054.60.1830.00000275617

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001740.000174
Ashkenazi Jewish0.002990.00298
East Asian0.0002780.000272
Finnish0.00004620.0000462
European (Non-Finnish)0.0002380.000237
Middle Eastern0.0002780.000272
South Asian0.0003610.000359
Other0.0004930.000489

dbNSFP

Source: dbNSFP

Function
FUNCTION: Cleaves the propeptides of type I and II collagen prior to fibril assembly. Does not act on type III collagen. May also play a role in development that is independent of its role in collagen biosynthesis.;
Disease
DISEASE: Ehlers-Danlos syndrome, dermatosparaxis type (EDSDERMS) [MIM:225410]: A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSDERMS is an autosomal recessive form characterized by extreme skin fragility and easy bruising, large fontanels, blue sclerae, puffy eyelids, micrognathia, umbilical hernia, and short fingers. Joint hypermobility becomes more important with age. {ECO:0000269|PubMed:10417273}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Collagen biosynthesis and modifying enzymes;Post-translational protein modification;Metabolism of proteins;Collagen formation;Extracellular matrix organization;O-glycosylation of TSR domain-containing proteins;O-linked glycosylation (Consensus)

Recessive Scores

pRec
0.315

Intolerance Scores

loftool
0.135
rvis_EVS
-1.8
rvis_percentile_EVS
2.22

Haploinsufficiency Scores

pHI
0.333
hipred
Y
hipred_score
0.685
ghis
0.589

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.213

Gene Damage Prediction

AllRecessiveDominant
MendelianHighMediumHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Adamts2
Phenotype
integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; craniofacial phenotype; reproductive system phenotype; normal phenotype; respiratory system phenotype; skeleton phenotype;

Gene ontology

Biological process
spermatogenesis;protein processing;collagen fibril organization;lung development;collagen catabolic process;skin development
Cellular component
extracellular region;collagen-containing extracellular matrix
Molecular function
metalloendopeptidase activity;metallopeptidase activity;zinc ion binding