ISG20L2

Chr 1

interferon stimulated exonuclease gene 20 like 2

Also known as: HSD38

NCBI Gene: 81875 ENSG00000143319 UniProt: Q9H9L3 OMIM: 611930

This gene encodes a 3'-5' exoribonuclease that may be involved in the processing of the 12S pre-rRNA. Pseudogenes have been identified on chromosomes 6 and 11. [provided by RefSeq, Dec 2014]

OMIM Research

This gene encodes a 3'-5' exoribonuclease that may be involved in the processing of the 12S pre-rRNA. Pseudogenes have been identified on chromosomes 6 and 11. [provided by RefSeq, Dec 2014]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.71

Clinical Summary— ISG20L2

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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

47 VUS of 56 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.71LOEUF

pLI 0.088

Z-score 2.30

OE 0.31 (0.15–0.71)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.81Z-score

OE missense 0.84 (0.74–0.95)

167 obs / 199.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.31 (0.15–0.71)

0≤0.351.4

Missense OE?0.84 (0.74–0.95)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 4 / 13.0Missense obs/exp: 167 / 199.1Syn Z: -0.09

This gene — mechanism propensity

0.7326th %ile

GOF

0.4973th %ile

LOF

0.4038th %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

56 submitted variants in ClinVar

ClinVar

Classification Summary

VUS47

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	32	15	0	47
Likely Benign	4	0	1	5
Benign	0	0	0	0
Total	36	15	1	52

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap ISG20L2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →