DSCAM

Chr 21

DS cell adhesion molecule

Also known as: CHD2, CHD2-42, CHD2-52

NCBI Gene: 1826 ENSG00000171587 UniProt: O60469 OMIM: 602523

DSCAM encodes a cell adhesion molecule that mediates neuronal self-avoidance, axon guidance, and lamina-specific synaptic connections in retinal and spinal cord development. Mutations cause autosomal dominant intellectual disability with behavioral abnormalities and seizures, typically presenting in early childhood. This gene is extremely intolerant to loss-of-function variants, indicating that proper dosage is critical for normal neurodevelopment.

OMIM ResearchSummary from RefSeq, UniProt

This gene is a member of the immunoglobulin superfamily of cell adhesion molecules (Ig-CAMs), and is involved in human central and peripheral nervous system development. This gene is a candidate for Down syndrome and congenital heart disease (DSCHD). A gene encoding a similar Ig-CAM protein is located on chromosome 11. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.19

Clinical Summary— DSCAM

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 222 VUS of 348 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.19LOEUF

pLI 1.000

Z-score 8.07

OE 0.11 (0.07–0.19)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.22Z-score

OE missense 0.74 (0.70–0.78)

889 obs / 1203.6 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.11 (0.07–0.19)

0≤0.351.4

Missense OE?0.74 (0.70–0.78)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 11 / 96.5Missense obs/exp: 889 / 1203.6Syn Z: -1.21

This gene — mechanism propensity

0.5378th %ile

GOF

0.5171th %ile

LOF

0.68top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 71% of P/LP variants are LoF · LOEUF 0.19

Literature Evidence

LOFStudy sequences 189 autism risk genes in a 1,543 Chinese ASD probands (1,045 from trios). Two de novo DSCAM disrupting variants (defined as nonsense, frameshift or splice site) in 1,086 Chinese ASD trios. Also one maternally inherited DSCAM disrupting variant (maternal phenotype unclear). Also, 20 m1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 27824329 ↗

ClinVar Variant Classifications

348 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic3

VUS222

Likely Benign88

Benign17

Conflicting1

Pathogenic

Likely Pathogenic

222

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	0	0	0	4
Likely Pathogenic	1	2	0	0	3
VUS	9	209	4	0	222
Likely Benign	0	33	3	52	88
Benign	0	1	1	15	17
Conflicting	—				1
Total	14	245	8	67	335

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

75 pathogenic / likely-pathogenic (of 89) ClinVar copy-number / structural variants overlap DSCAM — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →