22-37239015-A-G

Position:

• chr22-37239015-A-G

Variant summary

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

The ENST00000249071.11(RAC2):​c.107+2572T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,852 control chromosomes in the GnomAD database, including 12,696 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 (12696 hom., cov: 31)
• Consequence: RAC2 ENST00000249071.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC2	NM_002872.5	c.107+2572T>C		intron_variant		ENST00000249071.11	NP_002863.1
RAC2	XM_006724286.4	c.107+2572T>C		intron_variant			XP_006724349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000249071.11	c.107+2572T>C		intron_variant		1	NM_002872.5	ENSP00000249071	P1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61161 AN: 151734 Hom.: 12674 Cov.: 31

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.403 AC: 61224 AN: 151852 Hom.: 12696 Cov.: 31 AF XY: 0.400 AC XY: 29704 AN XY: 74214

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.406

Alfa AF: 0.378 Hom.: 22343

Bravo AF: 0.406

Asia WGS AF: 0.386 AC: 1342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.81

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: rs2284038; hg19: chr22-37635055;