ICE2

Chr 15

interactor of little elongation complex ELL subunit 2

Also known as: BRCC1, NARG2

NCBI Gene: 79664 ENSG00000128915 UniProt: Q659A1 OMIM: 610835

ICE2 encodes a component of the little elongation complex that regulates small nuclear RNA gene transcription by RNA polymerases II and III, with the protein localizing to Cajal bodies where ribonucleoprotein complexes assemble. Mutations cause neurodevelopmental disorder with growth retardation, seizures, and speech and language delay, inherited in an autosomal recessive pattern. The gene shows very low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed clinically.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein component of the little elongation complex (LEC), which plays a role in small nuclear RNA (snRNA) transcription. The LEC regulates snRNA transcription by enhancing both RNA Polymerase II occupancy and transcriptional elongation. The encoded protein and other LEC components have been shown to localize to Cajal bodies, which are sites of ribonucleoprotein (RNP) complex assembly. Pseudogenes of this gene have been identified on chromosomes 3 and 4. [provided by RefSeq, May 2017]

OMIM ResearchGenerating clinical summary…

LOEUF 0.84

Clinical Summary— ICE2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

146 VUS of 192 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.84LOEUF

pLI 0.000

Z-score 2.44

OE 0.61 (0.45–0.84)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.91Z-score

OE missense 1.11 (1.04–1.20)

554 obs / 497.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.61 (0.45–0.84)

0≤0.351.4

Missense OE?1.11 (1.04–1.20)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 28 / 45.8Missense obs/exp: 554 / 497.2Syn Z: -0.67

ClinVar Variant Classifications

192 submitted variants in ClinVar

ClinVar

Classification Summary

VUS146

Likely Benign18

Benign5

146

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	2	143	1	0	146
Likely Benign	0	9	2	7	18
Benign	0	2	0	3	5
Total	2	154	3	10	169

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap ICE2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →