22-37234443-T-C

Position:

• chr22-37234443-T-C

Variant summary

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

The NM_002872.5(RAC2):​c.108-1525A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,178 control chromosomes in the GnomAD database, including 1,012 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 0.11 (1012 hom., cov: 32)
• Consequence: RAC2 NM_002872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAC2	NM_002872.5	c.108-1525A>G		intron_variant		ENST00000249071.11
RAC2	XM_006724286.4	c.108-1525A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAC2	ENST00000249071.11	c.108-1525A>G		intron_variant		1	NM_002872.5	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16699 AN: 152058 Hom.: 1009 Cov.: 32

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0799

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.110 AC: 16713 AN: 152178 Hom.: 1012 Cov.: 32 AF XY: 0.110 AC XY: 8195 AN XY: 74388

Gnomad4 AFR AF: 0.0974

Gnomad4 AMR AF: 0.0799

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.124

Alfa AF: 0.112 Hom.: 162

Bravo AF: 0.108

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.55
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs9607432; hg19: chr22-37630483;