MCF2L2

Chr 3

MCF.2 cell line derived transforming sequence-like 2

Also known as: ARHGEF22

NCBI Gene: 23101 ENSG00000053524 UniProt: Q86YR7 OMIM: 619946

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.90

Clinical Summary— MCF2L2

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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

185 VUS of 221 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.90LOEUF

pLI 0.000

Z-score 2.20

OE 0.71 (0.56–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.79Z-score

OE missense 0.91 (0.85–0.98)

559 obs / 613.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.71 (0.56–0.90)

0≤0.351.4

Missense OE?0.91 (0.85–0.98)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 48 / 67.5Missense obs/exp: 559 / 613.8Syn Z: 1.70

This gene — mechanism propensity

0.6550th %ile

GOF

0.72top 25%

LOF

0.3164th %ile

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

GOFprediction above median

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

221 submitted variants in ClinVar

ClinVar

Classification Summary

VUS185

Likely Benign17

185

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	185	0	185
Likely Benign	15	2	17
Benign	0	0	0
Total	200	2	202

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

View in ClinVar →

37 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap MCF2L2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →