NM_002872.5:c.448+1169T>C

Variant names:

• chr22-37230062-A-G
• rs2284037
• NM_002872.5:c.448+1169T>C

Variant summary

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

The NM_002872.5(RAC2):​c.448+1169T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,814 control chromosomes in the GnomAD database, including 12,325 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 (12325 hom., cov: 31)
• Consequence: RAC2 NM_002872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591
• Publications: 11 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 = 0.441 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.448+1169T>C		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.448+1169T>C		intron	N/A	ENSP00000249071.6	P15153
	RAC2	ENST00000481215.1	TSL:1	n.273+1169T>C		intron	N/A
	RAC2	ENST00000870381.1		c.448+1169T>C		intron	N/A	ENSP00000540440.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60943 AN: 151694 Hom.: 12303 Cov.: 31

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.402 AC: 61010 AN: 151814 Hom.: 12325 Cov.: 31 AF XY: 0.397 AC XY: 29429 AN XY: 74174

African (AFR) AF: 0.447 AC: 18481 AN: 41356

American (AMR) AF: 0.359 AC: 5480 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1546 AN: 3468

East Asian (EAS) AF: 0.327 AC: 1682 AN: 5148

South Asian (SAS) AF: 0.332 AC: 1594 AN: 4804

European-Finnish (FIN) AF: 0.342 AC: 3610 AN: 10568

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27328 AN: 67900

Other (OTH) AF: 0.408 AC: 861 AN: 2110

Alfa AF: 0.396 Hom.: 6360

Bravo AF: 0.406

Asia WGS AF: 0.336 AC: 1168 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	1.9
DANN	Benign	0.47
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2284037; hg19: chr22-37626102;