Mendeliome
Gene: DSCAM Green List (high evidence)Green List (high evidence)
AR syndromic disorder characterised by moderate-severe neurodevelopmental delay, focal seizures, short stature, poor vision, nystagmus, and retinal dysfunction (6 individuals from 4 families).
PMID 42063257 - 4 new individuals from 3 unrelated families (one individual is sibling of case reported ion PMID 28600779), presenting with developmental delay (mod-severe), intellectual disability (mod-severe), early‑onset focal seizures, short stature (range -2 to -3.9SD), poor vision, congenital nystagmus and retinal dysfunction. WES/WGS identified biallelic LOF variants in DSCAM (nonsense, frameshift, exon duplications, splice). Heterozygote parents of individuals did not have any neurodevelopmental or ocular issues. DSCAM has low biological tolerance for both LoF and missense variation. Previous mouse and chicken DSCAM knock‑out models recapitulate the retinal phenotype (no allele‑specific rescue).
PMID 28600779 - 1 individual from consanguineous Saudi family with developmental delay, intellectual disability, short stature (-3.5SD), seizures, poor vision, nystagmus and retinal dysfunction. WES identified a homozygous splice site variant (c.4132+2T>A). Parental phenotype not provided.
PMID 33170561 - 1 individual from consanguineous family with global developmental delay, normal stature (-1SD), poor vision, nystagmus and retinopathy. WGS identified a homozygous 1.14Mb deletion at 21q22.2 removing DSCAM and 3 other genes.
NB: Green for biallelic, Amber for monoallelicCreated: 15 Jun 2026, 12:42 p.m. | Last Modified: 15 Jun 2026, 1:29 p.m.
Panel Version: 2.38
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Neurodevelopmental disorder (MONDO:0700092), DSCAM-related
Publications
I don't know
No OMIM gene disease association. Variants predominantly identified from large cohort studies with limited phenotypic information. Associations with ID, ASD, Hirschsprung disease reported. One homozygous splice site variant reported with no parental phenotypes provided.
PMID 34253863 Lim et al 2021 - 12 yo proband with severe autism spectrum disorder diagnosed age 3, de novo heterozygous c.2051 del p.(L684X) variant identified (absent from gnomAD). Skin fibroblast human iPSC cells generated from proband and healthy controls. Forebrain-like induced neuronal cells showed reduced mRNA expression for NMDA-R subunits.
PMID 28600779 Monies et al 2017 - Homozygous splice site variant identified in proband from consanguineous Saudi family. Proband had growth restriction, microcephaly, developmental delay. Parental phenotype not provided.
PMID 30095639 and PMID 23671607 - report association between DSCAM polymorphisms and Hirschsprung disease in Chinese and European populations.
PMID 27824329 Wang et al 2016 - 2 denovo mutations in mixed ID/ASD cohort of 1,045; including comparison of previously published cases 6 LOF out of 4,998 cases.
PMID 28191889 2 denovo LOF in 13,407 mixed ID/ASD cases plus 4 previosly published cases our ot 6158; conclude denovo LOF enriched in cases vs controls
PMID 21904980; mouse model – het LOF mice show hydrocephalus, decreased motor function and impaired motor learning ability,
Evidence for missense lacking currentlyCreated: 14 May 2022, 10:11 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Autism; ID
Publications
Phenotypes for gene: DSCAM were changed from Neurodevelopmental disorder (MONDO:0700092), DSCAM-related; Autism MONDO:0005260 to Neurodevelopmental disorder (MONDO:0700092), DSCAM-related; Autism MONDO:0005260
Phenotypes for gene: DSCAM were changed from Neurodevelopmental disorder (MONDO:0700092), DSCAM-related; Autism MONDO:0005260 to Neurodevelopmental disorder (MONDO:0700092), DSCAM-related; Autism MONDO:0005260
Phenotypes for gene: DSCAM were changed from Neurodevelopmental disorder (MONDO:0700092), DSCAM-related; Autism MONDO:0005260 to Neurodevelopmental disorder (MONDO:0700092), DSCAM-related; Autism MONDO:0005260
Phenotypes for gene: DSCAM were changed from Neurodevelopmental disorder (MONDO:0700092), DSCAM-related; Autism MONDO:0005260 to Neurodevelopmental disorder (MONDO:0700092), DSCAM-related; Autism MONDO:0005260
Phenotypes for gene: DSCAM were changed from Neurodevelopmental disorder (MONDO:0700092), DSCAM-related; Autism MONDO:0005260 to Neurodevelopmental disorder (MONDO:0700092), DSCAM-related; Autism MONDO:0005260
Phenotypes for gene: DSCAM were changed from Autism MONDO:0005260 to Neurodevelopmental disorder (MONDO:0700092), DSCAM-related; Autism MONDO:0005260
Publications for gene: DSCAM were set to 34253863; 32807774; 28600779; 21904980; 28191889; 27824329; 30095639; 23671607
Mode of inheritance for gene: DSCAM was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Gene: dscam has been classified as Green List (High Evidence).
Phenotypes for gene: DSCAM were changed from to Autism MONDO:0005260
Publications for gene: DSCAM were set to
Gene: dscam has been classified as Green List (High Evidence).
Mode of inheritance for gene: DSCAM was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gene: dscam has been classified as Amber List (Moderate Evidence).
gene: DSCAM was added gene: DSCAM was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: DSCAM was set to Unknown
If promoting or demoting a gene, please provide comments to justify a decision to move it.
Genes included in a Genomics England gene panel for a rare disease category (green list) should fit the criteria A-E outlined below.
These guidelines were developed as a combination of the ClinGen DEFINITIVE evidence for a causal role of the gene in the disease(a), and the Developmental Disorder Genotype-Phenotype (DDG2P) CONFIRMED DD Gene evidence level(b) (please see the original references provided below for full details). These help provide a guideline for expert reviewers when assessing whether a gene should be on the green or the red list of a panel.
A. There are plausible disease-causing mutations(i) within, affecting or encompassing an interpretable functional region(ii) of this gene identified in multiple (>3) unrelated cases/families with the phenotype(iii).
OR
B. There are plausible disease-causing mutations(i) within, affecting or encompassing cis-regulatory elements convincingly affecting the expression of a single gene identified in multiple (>3) unrelated cases/families with the phenotype(iii).
OR
C. As definitions A or B but in 2 or 3 unrelated cases/families with the phenotype, with the addition of convincing bioinformatic or functional evidence of causation e.g. known inborn error of metabolism with mutation in orthologous gene which is known to have the relevant deficient enzymatic activity in other species; existence of an animal model which recapitulates the human phenotype.
AND
D. Evidence indicates that disease-causing mutations follow a Mendelian pattern of causation appropriate for reporting in a diagnostic setting(iv).
AND
E. No convincing evidence exists or has emerged that contradicts the role of the gene in the specified phenotype.
(i)Plausible disease-causing mutations: Recurrent de novo mutations convincingly affecting gene function. Rare, fully-penetrant mutations - relevant genotype never, or very rarely, seen in controls. (ii) Interpretable functional region: ORF in protein coding genes miRNA stem or loop. (iii) Phenotype: the rare disease category, as described in the eligibility statement. (iv) Intermediate penetrance genes should not be included.
It’s assumed that loss-of-function variants in this gene can cause the disease/phenotype unless an exception to this rule is known. We would like to collect information regarding exceptions. An example exception is the PCSK9 gene, where loss-of-function variants are not relevant for a hypercholesterolemia phenotype as they are associated with increased LDL-cholesterol uptake via LDLR (PMID: 25911073).
If a curated set of known-pathogenic variants is available for this gene-phenotype, please contact us at panelapp@genomicsengland.co.uk
We classify loss-of-function variants as those with the following Sequence Ontology (SO) terms:
Term descriptions can be found on the PanelApp homepage and Ensembl.
If you are submitting this evaluation on behalf of a clinical laboratory please indicate whether you report variants in this gene as part of your current diagnostic practice by checking the box
Standardised terms were used to represent the gene-disease mode of inheritance, and were mapped to commonly used terms from the different sources. Below each of the terms is described, along with the equivalent commonly-used terms.
A variant on one allele of this gene can cause the disease, and imprinting has not been implicated.
A variant on the paternally-inherited allele of this gene can cause the disease, if the alternate allele is imprinted (function muted).
A variant on the maternally-inherited allele of this gene can cause the disease, if the alternate allele is imprinted (function muted).
A variant on one allele of this gene can cause the disease. This is the default used for autosomal dominant mode of inheritance where no knowledge of the imprinting status of the gene required to cause the disease is known. Mapped to the following commonly used terms from different sources: autosomal dominant, dominant, AD, DOMINANT.
A variant on both alleles of this gene is required to cause the disease. Mapped to the following commonly used terms from different sources: autosomal recessive, recessive, AR, RECESSIVE.
The disease can be caused by a variant on one or both alleles of this gene. Mapped to the following commonly used terms from different sources: autosomal recessive or autosomal dominant, recessive or dominant, AR/AD, AD/AR, DOMINANT/RECESSIVE, RECESSIVE/DOMINANT.
A variant on one allele of this gene can cause the disease, however a variant on both alleles of this gene can result in a more severe form of the disease/phenotype.
A variant in this gene can cause the disease in males as they have one X-chromosome allele, whereas a variant on both X-chromosome alleles is required to cause the disease in females. Mapped to the following commonly used term from different sources: X-linked recessive.
A variant in this gene can cause the disease in males as they have one X-chromosome allele. A variant on one allele of this gene may also cause the disease in females, though the disease/phenotype may be less severe and may have a later-onset than is seen in males. X-linked inactivation and mosaicism in different tissues complicate whether a female presents with the disease, and can change over their lifetime. This term is the default setting used for X-linked genes, where it is not known definitately whether females require a variant on each allele of this gene in order to be affected. Mapped to the following commonly used terms from different sources: X-linked dominant, x-linked, X-LINKED, X-linked.
The gene is in the mitochondrial genome and variants within this can cause this disease, maternally inherited. Mapped to the following commonly used term from different sources: Mitochondrial.
Mapped to the following commonly used terms from different sources: Unknown, NA, information not provided.
For example, if the mode of inheritance is digenic, please indicate this in the comments and which other gene is involved.