DSCAM

DS cell adhesion molecule, the group of Ig-like cell adhesion molecule family|MicroRNA protein coding host genes|Fibronectin type III domain containing|I-set domain containing

Basic information

Region (hg38): 21:40010998-40847158

Links

ENSG00000171587 ∙ NCBI:1826 ∙ OMIM:602523 ∙ HGNC:3039 ∙ Uniprot:O60469 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism spectrum disorder (Moderate), mode of inheritance: AD

ClinVar

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

• Inborn genetic diseases (74 variants)
• not provided (67 variants)
• DSCAM-related condition (8 variants)
• Intellectual disability (6 variants)
• See cases (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DSCAM 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				27	19	46
missense		1	80	14	1	96
nonsense	1	1	1			3
start loss						0
frameshift	1		2			3
inframe indel						0
splice donor/acceptor (+/-2bp)			2			2
splice region			3			3
non coding				1	1	2
Total	2	2	85	42	21

Variants in DSCAM

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

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

Position	Type	Phenotype	Significance	ClinVar
21-40013093-C-T		Inborn genetic diseases	Uncertain significance (Dec 06, 2021)
21-40013118-C-T		Inborn genetic diseases	Uncertain significance (Jul 14, 2021)
21-40013147-C-G		DSCAM-related disorder	Uncertain significance (Dec 22, 2022)
21-40013202-C-T			Likely benign (Apr 03, 2018)
21-40013206-G-C		Inborn genetic diseases	Likely benign (Jun 06, 2023)
21-40013231-T-C		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
21-40013250-C-T			Likely benign (Jun 06, 2018)
21-40042427-T-A		Inborn genetic diseases	Uncertain significance (Jan 04, 2024)
21-40042448-C-T		Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
21-40042468-AG-A			Uncertain significance (Jun 12, 2017)
21-40042531-C-G			Likely benign (Apr 16, 2018)
21-40042531-C-T			Likely benign (Mar 29, 2018)
21-40042542-T-C		Inborn genetic diseases	Uncertain significance (Apr 27, 2022)
21-40042597-G-A		DSCAM-related disorder	Benign (Dec 27, 2023)
21-40042603-G-A			Likely benign (Jun 01, 2023)
21-40042661-C-T		Inborn genetic diseases	Uncertain significance (Sep 28, 2022)
21-40042663-T-C			Benign/Likely benign (Jan 01, 2024)
21-40042669-T-G			Benign (Dec 31, 2019)
21-40044069-A-T		DSCAM-related disorder	Benign (Dec 21, 2023)
21-40044088-C-T		DSCAM-related disorder	Likely benign (Dec 04, 2019)
21-40044099-C-T		Intellectual disability • Inborn genetic diseases	Uncertain significance (Jun 28, 2022)
21-40044102-T-C		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
21-40044115-C-G		Inborn genetic diseases	Likely benign (Aug 17, 2022)
21-40044143-G-T		Inborn genetic diseases	Uncertain significance (Jul 09, 2021)
21-40044167-G-T		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DSCAM	protein_coding	protein_coding	ENST00000400454	33	836140

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.83e-8	124791	0	16	124807	0.0000641

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.22	889	1.20e+3	0.739	0.0000746	13080
Missense in Polyphen		293	480.74	0.60948		5089
Synonymous	-1.21	528	494	1.07	0.0000347	4061
Loss of Function	8.07	11	96.5	0.114	0.00000523	1068

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000288	0.000286
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000592	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.0000719	0.0000706
Middle Eastern	0.0000592	0.0000556
South Asian	0.00	0.00
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cell adhesion molecule that plays a role in neuronal self-avoidance. Promotes repulsion between specific neuronal processes of either the same cell or the same subtype of cells. Mediates within retinal amacrine and ganglion cell subtypes both isoneuronal self-avoidance for creating an orderly dendritic arborization and heteroneuronal self-avoidance to maintain the mosaic spacing between amacrine and ganglion cell bodies (PubMed:10925149). Receptor for netrin required for axon guidance independently of and in collaboration with the receptor DCC. In spinal chord development plays a role in guiding commissural axons projection and pathfinding across the ventral midline to reach the floor plate upon ligand binding (PubMed:18585357, PubMed:19196994). Enhances netrin-induced phosphorylation of PAK1 and FYN (PubMed:15169762). Mediates intracellular signaling by stimulating the activation of MAPK8 and MAP kinase p38 (PubMed:18585357, PubMed:19196994). Adhesion molecule that promotes lamina-specific synaptic connections in the retina: expressed in specific subsets of interneurons and retinal ganglion cells (RGCs) and promotes synaptic connectivity via homophilic interactions (By similarity). {ECO:0000250|UniProtKB:F1NY98, ECO:0000269|PubMed:10925149, ECO:0000269|PubMed:15169762, ECO:0000269|PubMed:18585357, ECO:0000269|PubMed:19196994}.
• Pathway: Developmental Biology;DSCAM interactions;FOXA1 transcription factor network;Netrin-1 signaling;Axon guidance;Validated nuclear estrogen receptor alpha network (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.0818
• rvis_EVS: -3.29
• rvis_percentile_EVS: 0.43

Haploinsufficiency Scores

• pHI: 0.157
• hipred: Y
• hipred_score: 0.775
• ghis: 0.626

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.405

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dscam
• Phenotype: growth/size/body region phenotype; cellular phenotype; muscle 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); hearing/vestibular/ear phenotype; craniofacial phenotype; vision/eye phenotype; reproductive 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); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype

Gene ontology

• Biological process: cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;negative regulation of cell adhesion;nervous system development;axon guidance;synapse assembly;locomotory behavior;retina layer formation;positive regulation of phosphorylation;dendrite morphogenesis;positive regulation of axon extension involved in axon guidance;post-embryonic retina morphogenesis in camera-type eye;camera-type eye photoreceptor cell differentiation;dendrite self-avoidance
• Cellular component: extracellular region;plasma membrane;integral component of plasma membrane;membrane;cell junction;axon;growth cone;synapse
• Molecular function: protein binding;cell-cell adhesion mediator activity