rs2239775

Variant names:

• chr22-37241801-C-A
• rs2239775
• NM_002872.5:c.36-143G>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.36-143G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 739,974 control chromosomes in the GnomAD database, including 9,234 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 0.17 (2534 hom., cov: 33)
  • Exomes 𝑓: 0.14 (6700 hom.)
• Consequence: RAC2 NM_002872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 17 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
• neutrophil immunodeficiency syndrome

  Inheritance: AD, Unknown Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia

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

ACMG classification

Our verdict: Benign. The variant received -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 = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002872.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC2	NM_002872.5	MANE Select	c.36-143G>T		intron	N/A	NP_002863.1	P15153

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC2	ENST00000249071.11	TSL:1 MANE Select	c.36-143G>T		intron	N/A	ENSP00000249071.6	P15153
	RAC2	ENST00000870381.1		c.36-143G>T		intron	N/A	ENSP00000540440.1
	RAC2	ENST00000870383.1		c.36-143G>T		intron	N/A	ENSP00000540442.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26368 AN: 152070 Hom.: 2524 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0771

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.145 AC: 85099 AN: 587786 Hom.: 6700 AF XY: 0.144 AC XY: 45744 AN XY: 316784

African (AFR) AF: 0.246 AC: 4006 AN: 16282

American (AMR) AF: 0.237 AC: 8291 AN: 35034

Ashkenazi Jewish (ASJ) AF: 0.0962 AC: 1919 AN: 19952

East Asian (EAS) AF: 0.131 AC: 4240 AN: 32488

South Asian (SAS) AF: 0.161 AC: 10460 AN: 64822

European-Finnish (FIN) AF: 0.0884 AC: 3528 AN: 39902

Middle Eastern (MID) AF: 0.133 AC: 357 AN: 2690

European-Non Finnish (NFE) AF: 0.137 AC: 47390 AN: 345156

Other (OTH) AF: 0.156 AC: 4908 AN: 31460

GnomAD4 genome AF: 0.174 AC: 26415 AN: 152188 Hom.: 2534 Cov.: 33 AF XY: 0.170 AC XY: 12669 AN XY: 74414

African (AFR) AF: 0.254 AC: 10553 AN: 41494

American (AMR) AF: 0.214 AC: 3273 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3472

East Asian (EAS) AF: 0.154 AC: 800 AN: 5182

South Asian (SAS) AF: 0.153 AC: 738 AN: 4826

European-Finnish (FIN) AF: 0.0771 AC: 818 AN: 10610

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9455 AN: 67994

Other (OTH) AF: 0.154 AC: 326 AN: 2112

Alfa AF: 0.155 Hom.: 1733

Bravo AF: 0.187

Asia WGS AF: 0.172 AC: 596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.086
DANN	Benign	0.54
PhyloP100		-1.8
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: rs2239775; hg19: chr22-37637841; COSMIC: COSV107218465;