VGLL2

Chr 6

vestigial like family member 2

Also known as: VGL2, VITO1

NCBI Gene: 245806ENSG00000170162UniProt: Q8N8G2

This gene encodes a protein with a transcriptional enhancer factor 1 (TEF-1) interaction domain. The encoded protein may act as a co-factor of TEF-1 regulated gene expression during skeletal muscle development. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Jul 2012]

94
ClinVar variants
27
Pathogenic / LP
0.71
pLI score
0
Active trials
Clinical Summary— VGLL2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.71) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 63 VUS of 94 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.57LOEUF
pLI 0.705
Z-score 2.35
OE 0.12 (0.04–0.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.12Z-score
OE missense 0.97 (0.84–1.13)
121 obs / 124.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.12 (0.04–0.57)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.84–1.13)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 1 / 8.3Missense obs/exp: 121 / 124.7Syn Z: 0.44

ClinVar Variant Classifications

94 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic6
VUS63
Likely Benign1
Benign3
21
Pathogenic
6
Likely Pathogenic
63
VUS
1
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
6
0
6
VUS
0
60
3
0
63
Likely Benign
0
0
0
1
1
Benign
0
2
0
1
3
Total06230294

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

View in ClinVar →

Protein Context — Lollipop Plot

VGLL2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
VESTIGIAL-LIKE 2; VGLL2
MIM #609979 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Congenital spindle cell rhabdomyosarcoma.
Whittle SB et al.·Pediatr Blood Cancer
2019Review
VGLL2-NCOA2 leverages developmental programs for pediatric sarcomagenesis.
Watson S et al.·Cell Rep
2023
Molecular diagnostics in the management of rhabdomyosarcoma.
Arnold MA et al.·Expert Rev Mol Diagn
2017Review
The current landscape of rhabdomyosarcomas: an update.
Leiner J et al.·Virchows Arch
2020Review
Congenital spindle cell rhabdomyosarcoma: An international cooperative analysis.
Whittle S et al.·Eur J Cancer
2022
Infantile Rhabdomyosarcomas With VGLL2 Rearrangement Are Not Always an Indolent Disease: A Study of 4 Aggressive Cases With Clinical, Pathologic, Molecular, and Radiologic Findings.
Cyrta J et al.·Am J Surg Pathol
2021Case report
A Molecular Study of Pediatric Spindle and Sclerosing Rhabdomyosarcoma: Identification of Novel and Recurrent VGLL2-related Fusions in Infantile Cases.
Alaggio R et al.·Am J Surg Pathol
2016Cohort
Functional Genomics of Novel Rhabdomyosarcoma Fusion-Oncogenes Using Zebrafish.
Kent MR et al.·Methods Mol Biol
2024Functional
Spindle Cell/Sclerosing Rhabdomyosarcoma With PAX8::PPARG Fusion.
Rakheja D et al.·Int J Surg Pathol
2022Case report
FGFR1 fusions as a novel molecular driver in rhabdomyosarcoma.
de Traux De Wardin H et al.·Genes Chromosomes Cancer
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools