SCYL2

SCY1 like pseudokinase 2, the group of SCY1 like pseudokinases|Armadillo like helical domain containing

Basic information

Region (hg38): 12:100267140-100341715

Links

ENSG00000136021 ∙ NCBI:55681 ∙ OMIM:616365 ∙ HGNC:19286 ∙ Uniprot:Q6P3W7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum (Moderate), mode of inheritance: AR
• arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum	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	Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	31960134

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SCYL2 gene.

• Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum (2 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCYL2 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				1	1	2
missense			64	3		67
nonsense	2		1			3
start loss						0
frameshift		3	1			4
inframe indel	1					1
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding					2	2
Total	3	3	66	4	3

Highest pathogenic variant AF is 0.00000657

Variants in SCYL2

This is a list of pathogenic ClinVar variants found in the SCYL2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-100283066-TG-T		Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum	Likely pathogenic (May 26, 2021)
12-100283074-G-T		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
12-100283076-C-G		Inborn genetic diseases	Uncertain significance (Aug 20, 2024)
12-100283076-C-T		Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum	Pathogenic (Mar 17, 2024)
12-100283082-A-G		Inborn genetic diseases	Uncertain significance (Feb 28, 2024)
12-100283091-G-A		Inborn genetic diseases	Uncertain significance (Mar 23, 2022)
12-100283098-A-G		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)
12-100283145-C-G		Inborn genetic diseases	Uncertain significance (Dec 03, 2024)
12-100283145-C-CA		Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum	Likely pathogenic (May 26, 2021)
12-100283146-A-G		Inborn genetic diseases	Uncertain significance (May 21, 2024)
12-100283182-C-A		Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum	Benign (Jul 15, 2021)
12-100291527-A-G		Inborn genetic diseases	Uncertain significance (Dec 10, 2024)
12-100291538-TGACAAGTATCAAAAATTTGAA-T		Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum	Pathogenic (Jan 01, 2021)
12-100291623-C-T		Inborn genetic diseases	Pathogenic (Jul 07, 2022)
12-100298141-T-C			Uncertain significance (Jan 18, 2024)
12-100311092-G-A		Inborn genetic diseases	Uncertain significance (Jul 05, 2022)
12-100311107-G-C		Inborn genetic diseases	Uncertain significance (Jun 02, 2024)
12-100311134-G-A		Inborn genetic diseases	Uncertain significance (Nov 21, 2022)
12-100311156-A-AT		Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum	Likely pathogenic (Feb 14, 2023)
12-100311187-A-T		Inborn genetic diseases	Uncertain significance (Mar 18, 2024)
12-100312467-A-G			Likely benign (Jun 01, 2022)
12-100312519-T-G			Uncertain significance (Jan 18, 2024)
12-100312547-T-C		Inborn genetic diseases	Uncertain significance (May 03, 2023)
12-100312552-T-G		Inborn genetic diseases	Uncertain significance (Jan 09, 2024)
12-100313428-C-T		Inborn genetic diseases	Uncertain significance (Dec 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SCYL2	protein_coding	protein_coding	ENST00000360820	17	74585

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0771	0.923	125724	0	23	125747	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.25	389	465	0.837	0.0000217	6151
Missense in Polyphen		62	103.12	0.60126		1478
Synonymous	0.387	153	159	0.961	0.00000771	1734
Loss of Function	4.56	11	43.4	0.253	0.00000215	549

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000126	0.000124
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.00	0.00
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000151	0.000149
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of AP2-containing clathrin coated structures at the plasma membrane or of endocytic coated vesicles. According to PubMed:15809293, probable serine/threonine-protein kinase that phosphorylates, in vitro, the beta2-subunit of the plasma membrane adapter complex AP2 and other proteins in presence of poly-L- lysine. According to PubMed:16914521, has no detectable kinase activity in vitro. May regulate clathrin-dependent trafficking between the TGN and/or the endosomal system. {ECO:0000269|PubMed:15809293, ECO:0000269|PubMed:16914521}.

Recessive Scores

• pRec: 0.193

Intolerance Scores

• loftool: 0.376
• rvis_EVS: 0.04
• rvis_percentile_EVS: 57.41

Haploinsufficiency Scores

• pHI: 0.248
• hipred: Y
• hipred_score: 0.544
• ghis: 0.594

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.924

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Scyl2
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal 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); reproductive system phenotype; growth/size/body region phenotype; hematopoietic system phenotype; cellular phenotype

Gene ontology

• Biological process: positive regulation of receptor internalization;protein phosphorylation;endosome to lysosome transport;negative regulation of canonical Wnt signaling pathway;receptor internalization involved in canonical Wnt signaling pathway;positive regulation of clathrin-dependent endocytosis
• Cellular component: Golgi apparatus;endosome membrane;clathrin-coated vesicle;perinuclear region of cytoplasm
• Molecular function: protein kinase activity;signaling receptor binding;protein binding;ATP binding