rs13058338

Variant names:

• chr22-37236730-T-A
• rs13058338
• NM_002872.5:c.108-3812A>T

Your query was ambiguous. Multiple possible variants found:

• chr22-37236730-T-A
• chr22-37236730-T-G

Variant summary

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

The NM_002872.5(RAC2):​c.108-3812A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 151,916 control chromosomes in the GnomAD database, including 3,350 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 0.20 (3350 hom., cov: 32)
• Consequence: RAC2 NM_002872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 58 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 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.108-3812A>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.108-3812A>T		intron	N/A	ENSP00000249071.6	P15153
	RAC2	ENST00000870381.1		c.108-3812A>T		intron	N/A	ENSP00000540440.1
	RAC2	ENST00000870383.1		c.108-3812A>T		intron	N/A	ENSP00000540442.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30491 AN: 151796 Hom.: 3349 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0885

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.201 AC: 30511 AN: 151916 Hom.: 3350 Cov.: 32 AF XY: 0.199 AC XY: 14809 AN XY: 74252

African (AFR) AF: 0.113 AC: 4672 AN: 41436

American (AMR) AF: 0.222 AC: 3395 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3462

East Asian (EAS) AF: 0.0887 AC: 457 AN: 5154

South Asian (SAS) AF: 0.208 AC: 1003 AN: 4814

European-Finnish (FIN) AF: 0.221 AC: 2322 AN: 10512

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17281 AN: 67946

Other (OTH) AF: 0.203 AC: 427 AN: 2108

Alfa AF: 0.113 Hom.: 205

Bravo AF: 0.197

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.87
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13058338; hg19: chr22-37632770;