ADAMTSL2

ADAMTS like 2, the group of ADAMTS like

Basic information

Region (hg38): 9:133532164-133575519

Links

ENSG00000197859 ∙ NCBI:9719 ∙ OMIM:612277 ∙ HGNC:14631 ∙ Uniprot:Q86TH1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• geleophysic dysplasia 1 (Strong), mode of inheritance: AR
• Ehlers-Danlos syndrome (Limited), mode of inheritance: AD
• geleophysic dysplasia 1 (Strong), mode of inheritance: AR
• geleophysic dysplasia 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Geleophysic dysplasia 1	AR	Cardiovascular	The disorder may frequently be clinically recognizable, but individuals can have cardiovascular manifestations such as progressive cardiac valve thickening necessitating surgical interventions very early in childhood, and early diagnosis may be beneficial to allow early treatment	Biochemical; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal	18677313; 21415077; 21683322; 20301776

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADAMTSL2 gene.

• Geleophysic_dysplasia_1 (115 variants)
• Inborn_genetic_diseases (80 variants)
• not_provided (49 variants)
• ADAMTSL2-related_disorder (22 variants)
• Lethal_short-limb_skeletal_dysplasia,_Al_Gazali_type (14 variants)
• not_specified (3 variants)
• Geleophysic_dysplasia (3 variants)
• Abnormal_facial_shape (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADAMTSL2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014694.4. 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			33	21		54
missense	4	9	122	9		144
nonsense	2	4				6
start loss						0
frameshift		2				2
splice donor/acceptor (+/-2bp)	1	1	1			3
Total	7	16	156	30	0

Highest pathogenic variant AF is 0.0000148728

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADAMTSL2	protein_coding	protein_coding	ENST00000354484	18	43356

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00160	0.993	125739	0	8	125747	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.25	185	239	0.773	0.0000167	6245
Missense in Polyphen		49	93.051	0.52659		2292
Synonymous	-1.83	136	111	1.22	0.00000919	1861
Loss of Function	2.43	8	19.6	0.408	0.00000102	519

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.0000266	0.0000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Geleophysic dysplasia 1 (GPHYSD1) [MIM:231050]: An autosomal recessive disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. Radiologic features include delayed bone age, cone- shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have characteristic facial features including a 'happy' face with full cheeks, shortened nose, hypertelorism, long and flat philtrum, and thin upper lip. Other distinctive features include progressive cardiac valvular thickening often leading to an early death, toe walking, tracheal stenosis, respiratory insufficiency, and lysosomal-like storage vacuoles in various tissues. {ECO:0000269|PubMed:18677313, ECO:0000269|PubMed:21415077}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Post-translational protein modification;Metabolism of proteins;O-glycosylation of TSR domain-containing proteins;O-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.115

Haploinsufficiency Scores

• pHI: 0.260
• hipred: N
• hipred_score: 0.289
• ghis: 0.541

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.247

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adamtsl2
• Phenotype: respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype

Gene ontology

• Biological process: proteolysis;extracellular matrix organization;negative regulation of transforming growth factor beta receptor signaling pathway;lobar bronchus epithelium development
• Cellular component: extracellular matrix
• Molecular function: protein binding;peptidase activity;microfibril binding