rs2239773

Variant names:

• chr22-37242249-G-A
• rs2239773
• NM_002872.5:c.36-591C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002872.5(RAC2):​c.36-591C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,068 control chromosomes in the GnomAD database, including 4,546 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 0.24 (4546 hom., cov: 32)
• Consequence: RAC2 NM_002872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 12 publications found

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]

RAC2 Gene-Disease associations (from GenCC):

• immunodeficiency 73b with defective neutrophil chemotaxis and lymphopenia

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen
• immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• neutrophil immunodeficiency syndrome

  Inheritance: Unknown, AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC2	NM_002872.5	c.36-591C>T		intron_variant	Intron 1 of 6	ENST00000249071.11	NP_002863.1
RAC2	XM_006724286.4	c.36-591C>T		intron_variant	Intron 1 of 5		XP_006724349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000249071.11	c.36-591C>T		intron_variant	Intron 1 of 6	1	NM_002872.5	ENSP00000249071.6

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36921 AN: 151950 Hom.: 4548 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0890

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.243 AC: 36944 AN: 152068 Hom.: 4546 Cov.: 32 AF XY: 0.239 AC XY: 17765 AN XY: 74328

African (AFR) AF: 0.242 AC: 10023 AN: 41476

American (AMR) AF: 0.240 AC: 3665 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3468

East Asian (EAS) AF: 0.0892 AC: 462 AN: 5178

South Asian (SAS) AF: 0.209 AC: 1008 AN: 4822

European-Finnish (FIN) AF: 0.228 AC: 2411 AN: 10570

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17871 AN: 67962

Other (OTH) AF: 0.243 AC: 513 AN: 2114

Alfa AF: 0.253 Hom.: 5178

Bravo AF: 0.242

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.65
DANN	Benign	0.30
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2239773; hg19: chr22-37638289;