EPS8L2

Chr 11AR

EPS8 signaling adaptor L2

Also known as: DFNB106, EPS8R2

NCBI Gene: 64787 ENSG00000177106 UniProt: Q9H6S3 OMIM: 614988

This gene encodes a member of the EPS8 gene family. The encoded protein, like other members of the family, is thought to link growth factor stimulation to actin organization, generating functional redundancy in the pathways that regulate actin cytoskeletal remodeling. [provided by RefSeq, Dec 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.631 OMIM phenotype

Clinical Summary— EPS8L2

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Gene-Disease Validity (ClinGen)

nonsyndromic genetic hearing loss · ARModerate

Moderate evidence — consider for supplementary testing

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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

26 unique Pathogenic / Likely Pathogenic· 204 VUS of 438 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?

0.63LOEUF

pLI 0.000

Z-score 3.44

OE 0.42 (0.28–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.80Z-score

OE missense 1.11 (1.03–1.20)

451 obs / 405.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.42 (0.28–0.63)

0≤0.351.4

Missense OE?1.11 (1.03–1.20)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 17 / 40.6Missense obs/exp: 451 / 405.7Syn Z: -1.94

This gene — mechanism propensity

0.6261th %ile

GOF

0.6149th %ile

LOF

0.3551th %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

438 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18

Likely Pathogenic8

VUS204

Likely Benign148

Benign37

Conflicting6

Pathogenic

Likely Pathogenic

204

VUS

148

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	18	0	0	0	18
Likely Pathogenic	7	1	0	0	8
VUS	0	196	7	1	204
Likely Benign	1	7	66	74	148
Benign	0	2	30	5	37
Conflicting	—				6
Total	26	206	103	80	421

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap EPS8L2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →