GNAI2

Overview

Mutations in the GNAI2 gene, which encodes the G protein alpha subunit involved in signal transduction, have been identified as significant contributors to the pathogenesis of B-cell lymphomas, including BL, DLBCL and, to a lesser extent, FL.¹ Mutations in GNAI2, along with GNA13 and other small GTPases, affect the signaling pathways that regulate B-cell homing. These mutations are thought to cause aberrant localization and function of B-cells within lymphoid tissues.¹ The functional role of these mutations has not been studied as extensively as those in GNA13 and further work is needed to elucidate the specific role of these mutations in lymphomagenesis.

Relevance tier by entity

Entity	Tier	Description
BL	1	high-confidence BL gene
DLBCL	1	high-confidence DLBCL gene
FL	1	high-confidence FL gene

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	11.32
BL	Thomas cohort	9.70
BL	Panea cohort	8.90
DLBCL	GAMBL genomes	5.35
DLBCL	Schmitz cohort	6.38
DLBCL	Reddy cohort	1.90
DLBCL	Chapuy cohort	3.85
FL	GAMBL genomes	4.16

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	No	Yes	18.304	0.000
DLBCL	No	Yes	32.161	57.623
FL	No	Yes	55.205	0.000

[!NOTE] First described in BL in 2019 by Grande BM. First described in DLBCL in 2013 by Morin RD

## GNAI2 Hotspots

Chromosome	Coordinate (hg19)	ref>alt	HGVSp
chr3	50289532	G>A	G40D
chr3	50289546	G>T	G45W
chr3	50289547	G>A	G45E
chr3	50289553	G>A	S47N
chr3	50289554	C>G	S47R
chr3	50289555	A>C	T48P
chr3	50289568	A>G	Q52R
chr3	50293686	T>G	L176R
chr3	50293695	G>A	R179H
chr3	50293698	T>A	V180E
chr3	50293703	A>G	T182A

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

References

1. Morin RD, Mungall K, Pleasance E, Mungall AJ, Goya R, Huff RD, Scott DW, Ding J, Roth A, Chiu R, Corbett RD, Chan FC, Mendez-Lago M, Trinh DL, Bolger-Munro M, Taylor G, Hadj Khodabakhshi A, Ben-Neriah S, Pon J, Meissner B, Woolcock B, Farnoud N, Rogic S, Lim EL, Johnson NA, Shah S, Jones S, Steidl C, Holt R, Birol I, Moore R, Connors JM, Gascoyne RD, Marra MA. Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing. Blood. 2013 Aug 15;122(7):1256-65. doi: 10.1182/blood-2013-02-483727. Epub 2013 May 22. PMID: 23699601; PMCID: PMC3744992.