PRRC2C

Chr 1

proline rich coiled-coil 2C

Also known as: BAT2-iso, BAT2D1, BAT2L2, XTP2

NCBI Gene: 23215 ENSG00000117523 UniProt: Q9Y520 OMIM: 617373

The PRRC2C protein binds RNA and is required for efficient formation of stress granules in the cytosol during cellular stress responses. Mutations cause autosomal recessive intellectual disability with microcephaly, seizures, and developmental delay, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely not tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity. Involved in stress granule assembly. Located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.12

Clinical Summary— PRRC2C

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

307 VUS of 390 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.12LOEUF

pLI 1.000

Z-score 10.19

OE 0.07 (0.04–0.12)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.49Z-score

OE missense 0.81 (0.77–0.85)

1155 obs / 1419.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.07 (0.04–0.12)

0≤0.351.4

Missense OE?0.81 (0.77–0.85)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 10 / 140.1Missense obs/exp: 1155 / 1419.5Syn Z: -1.00

This gene — mechanism propensity

0.2199th %ile

GOF

0.1999th %ile

LOF

0.87top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.12

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

390 submitted variants in ClinVar

ClinVar

Classification Summary

VUS307

Likely Benign21

307

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	306	0	307
Likely Benign	0	14	7	21
Benign	0	0	0	0
Total	1	320	7	328

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap PRRC2C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →