CWC22

Chr 2

CWC22 spliceosome associated protein

Also known as: EIF4GL, NCM, fSAPb

NCBI Gene: 57703 ENSG00000163510 UniProt: Q9HCG8 OMIM: 615186

Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in cytosol and nuclear speck. Part of U2-type catalytic step 1 spliceosome; U2-type catalytic step 2 spliceosome; and U2-type precatalytic spliceosome. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.47

Clinical Summary— CWC22

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

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ClinVar Variants

120 VUS of 150 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.001

Z-score 4.50

OE 0.31 (0.20–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.02Z-score

OE missense 0.86 (0.79–0.94)

384 obs / 444.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.31 (0.20–0.47)

0≤0.351.4

Missense OE?0.86 (0.79–0.94)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 15 / 48.9Missense obs/exp: 384 / 444.2Syn Z: 0.90

This gene — mechanism propensity

0.6162th %ile

GOF

0.5072th %ile

LOF

0.4233th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

150 submitted variants in ClinVar

ClinVar

Classification Summary

VUS120

Likely Benign7

Benign4

120

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	119	0	0	120
Likely Benign	0	6	0	1	7
Benign	1	1	1	1	4
Total	2	126	1	2	131

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap CWC22 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →