rs2239774

chr22-37241613-G-Cchr22-37241613-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002872.5(RAC2):c.81C>G(p.Ala27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,613,244 control chromosomes in the GnomAD database, including 18,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A27A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.16 (2025 hom., cov: 33)
  • Exomes 𝑓: 0.15 (16179 hom.)
• Consequence: RAC2 NM_002872.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.80

Genes affected

RAC2 (HGNC:9802): (Rac family small GTPase 2) This gene encodes a member of the Ras superfamily of small guanosine triphosphate (GTP)-metabolizing proteins. The encoded protein localizes to the plasma membrane, where it regulates diverse processes, such as secretion, phagocytosis, and cell polarization. Activity of this protein is also involved in the generation of reactive oxygen species. Mutations in this gene are associated with neutrophil immunodeficiency syndrome. There is a pseudogene for this gene on chromosome 6. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 22-37241613-G-C is Benign according to our data. Variant chr22-37241613-G-C is described in ClinVar as [Benign]. Clinvar id is 138865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-37241613-G-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.8 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAC2	NM_002872.5	c.81C>G	p.Ala27=	synonymous_variant	2/7	ENST00000249071.11
RAC2	XM_006724286.4	c.81C>G	p.Ala27=	synonymous_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAC2	ENST00000249071.11	c.81C>G	p.Ala27=	synonymous_variant	2/7	1	NM_002872.5	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24055 AN: 152100 Hom.: 2018 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.166

GnomAD3 exomes AF: 0.153 AC: 38543 AN: 251480 Hom.: 3230 AF XY: 0.157 AC XY: 21326 AN XY: 135914

Gnomad AFR exome AF: 0.185

Gnomad AMR exome AF: 0.0803

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.276

Gnomad SAS exome AF: 0.181

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.146 AC: 212904 AN: 1461022 Hom.: 16179 Cov.: 33 AF XY: 0.147 AC XY: 106966 AN XY: 726864

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.0873

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.158 AC: 24081 AN: 152222 Hom.: 2025 Cov.: 33 AF XY: 0.159 AC XY: 11820 AN XY: 74428

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.170

Alfa AF: 0.117 Hom.: 436

Bravo AF: 0.159

Asia WGS AF: 0.219 AC: 762 AN: 3478

EpiCase AF: 0.150

EpiControl AF: 0.152

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Neutrophil immunodeficiency syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 07, 2013

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Immunodeficiency 73b with defective neutrophil chemotaxis and lymphopenia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	13
Dann	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2239774; hg19: chr22-37637653; COSMIC: COSV50774221;