rs2284037

chr22-37230062-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002872.5(RAC2):c.448+1169T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,814 control chromosomes in the GnomAD database, including 12,325 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12325 hom., cov: 31)
• Consequence: RAC2 NM_002872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAC2	NM_002872.5	c.448+1169T>C		intron_variant		ENST00000249071.11
RAC2	XM_006724286.4	c.448+1169T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAC2	ENST00000249071.11	c.448+1169T>C		intron_variant		1	NM_002872.5	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60943 AN: 151694 Hom.: 12303 Cov.: 31

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.410

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.402 AC: 61010 AN: 151814 Hom.: 12325 Cov.: 31 AF XY: 0.397 AC XY: 29429 AN XY: 74174

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.408

Alfa AF: 0.393 Hom.: 5629

Bravo AF: 0.406

Asia WGS AF: 0.336 AC: 1168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.9
Dann	Benign	0.47

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: rs2284037; hg19: chr22-37626102;