CCDC50

Chr 3AD

coiled-coil domain containing 50

ENSG00000152492 UniProt: Q8IVM0 OMIM: 611051

Involved in EGFR signaling

OMIM Research

Involved in EGFR signaling

OMIM ResearchGenerating clinical summary…

MultiplemechanismADLOEUF 0.741 OMIM phenotype

Clinical Summary— CCDC50

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Gene-Disease Validity (ClinGen)

nonsyndromic genetic hearing loss · ADLimited

Limited evidence — not for standalone diagnostic reporting

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.000

Z-score 2.70

OE 0.49 (0.33–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.07Z-score

OE missense 0.99 (0.89–1.09)

258 obs / 261.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.33–0.74)

0≤0.351.4

Missense OE?0.99 (0.89–1.09)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 16 / 32.7Missense obs/exp: 258 / 261.3Syn Z: -0.17

This gene — mechanism propensity

0.82top 10%

GOF

0.6931th %ile

LOF

0.2091th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median · 1 literature citation

GOFprediction above median · 1 literature citation

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.

Literature Evidence

DNTaken together the in vivo and in vitro results obtained in this study suggest that the two Spanish mutations in CCDC50 exert their effect through a dominant-negative or gain of function mechanism rather than by haploinsufficiency.1

GOFTaken together the in vivo and in vitro results obtained in this study suggest that the two Spanish mutations in CCDC50 exert their effect through a dominant-negative or gain of function mechanism rather than by haploinsufficiency.1

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

References