ADAMTSL2

ADAMTS like 2, the group of ADAMTS like

Basic information

Region (hg38): 9:133532163-133575519

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

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 (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.

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			33	10	4	47
missense		6	94	6		106
nonsense	1	4				5
start loss						0
frameshift		2		1		3
inframe indel			2			2
splice donor/acceptor (+/-2bp)		1	1			2
splice region			4	2		6
non coding			25	11	41	77
Total	1	13	155	28	45

Variants in ADAMTSL2

This is a list of pathogenic ClinVar variants found in the ADAMTSL2 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-133534854-G-GC		Geleophysic dysplasia	Likely benign (Jun 14, 2016)
9-133534919-T-C		Lethal short-limb skeletal dysplasia, Al Gazali type	Uncertain significance (Oct 11, 2022)
9-133536303-G-A			Benign (Jun 19, 2018)
9-133536322-C-G			Benign (Jun 29, 2019)
9-133536322-C-T			Likely benign (Jul 09, 2018)
9-133536484-A-C		Geleophysic dysplasia 1	Benign (Jul 14, 2021)
9-133536566-C-G		Geleophysic dysplasia 1	Uncertain significance (Jan 13, 2018)
9-133536623-G-C		Geleophysic dysplasia 1	Uncertain significance (Apr 27, 2017)
9-133536723-G-C		Geleophysic dysplasia 1	Uncertain significance (Feb 01, 2022)
9-133536770-G-A		Geleophysic dysplasia 1 • ADAMTSL2-related disorder	Conflicting classifications of pathogenicity (Oct 01, 2023)
9-133536785-G-T		Inborn genetic diseases	Uncertain significance (Mar 15, 2024)
9-133536793-C-T		Geleophysic dysplasia 1	Uncertain significance (Jan 13, 2018)
9-133536800-A-G			Likely benign (May 21, 2015)
9-133536945-G-T			Benign (Jun 28, 2018)
9-133537223-T-A			Benign (Jun 19, 2018)
9-133537400-C-T		ADAMTSL2-related disorder	Likely benign (Nov 10, 2023)
9-133537415-C-A		ADAMTSL2-related disorder	Uncertain significance (Nov 10, 2023)
9-133537419-A-G		ADAMTSL2-related disorder	Likely benign (Aug 06, 2019)
9-133537436-G-C		Inborn genetic diseases	Uncertain significance (Nov 06, 2023)
9-133537468-GAGTGGACCA-G			Uncertain significance (Apr 20, 2023)
9-133537471-T-C		Lethal short-limb skeletal dysplasia, Al Gazali type	Uncertain significance (Oct 11, 2022)
9-133537529-G-A		Geleophysic dysplasia 1	Pathogenic (Jun 01, 2011)
9-133537543-C-T		Lethal short-limb skeletal dysplasia, Al Gazali type	Likely pathogenic (Oct 11, 2022)
9-133537551-C-T		ADAMTSL2-related disorder	Likely benign (Jul 30, 2019)
9-133538347-A-G		Geleophysic dysplasia 1	Pathogenic (Jun 17, 2017)

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