rs2239774

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002872.5(RAC2):c.81C>G(p.Ala27Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,613,244 control chromosomes in the GnomAD database, including 18,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A27A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.16 ( 2025 hom., cov: 33)

Exomes 𝑓: 0.15 ( 16179 hom. )

Consequence

RAC2
NM_002872.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.80

Publications

32 publications found

Variant links:

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)

RAC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 22-37241613-G-C is Benign according to our data. Variant chr22-37241613-G-C is described in ClinVar as Benign. ClinVar VariationId is 138865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.8 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC2	NM_002872.5 link	c.81C>G	p.Ala27Ala	synonymous_variant	Exon 2 of 7	ENST00000249071.11	NP_002863.1
RAC2	XM_006724286.4 link	c.81C>G	p.Ala27Ala	synonymous_variant	Exon 2 of 6		XP_006724349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000249071.11 link	c.81C>G	p.Ala27Ala	synonymous_variant	Exon 2 of 7	1	NM_002872.5	ENSP00000249071.6

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

24055

AN:

152100

Hom.:

2018

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.166

GnomAD2 exomes

AF:

0.153

AC:

38543

AN:

251480

AF XY:

0.157

show subpopulations

Gnomad AFR exome

AF:

0.185

Gnomad AMR exome

AF:

0.0803

Gnomad ASJ exome

AF:

0.195

Gnomad EAS exome

AF:

0.276

Gnomad FIN exome

AF:

0.135

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.146

AC:

212904

AN:

1461022

Hom.:

16179

Cov.:

AF XY:

0.147

AC XY:

106966

AN XY:

726864

show subpopulations

African (AFR)

AF:

0.188

AC:

6281

AN:

33448

American (AMR)

AF:

0.0873

AC:

3904

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

4987

AN:

26120

East Asian (EAS)

AF:

0.225

AC:

8948

AN:

39690

South Asian (SAS)

AF:

0.181

AC:

15620

AN:

86234

European-Finnish (FIN)

AF:

0.133

AC:

7079

AN:

53412

Middle Eastern (MID)

AF:

0.181

AC:

1041

AN:

5764

European-Non Finnish (NFE)

AF:

0.140

AC:

155116

AN:

1111272

Other (OTH)

AF:

0.164

AC:

9928

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

10073

20146

30218

40291

50364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5696

11392

17088

22784

28480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.158

AC:

24081

AN:

152222

Hom.:

2025

Cov.:

AF XY:

0.159

AC XY:

11820

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.185

AC:

7693

AN:

41518

American (AMR)

AF:

0.114

AC:

1745

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

668

AN:

3468

East Asian (EAS)

AF:

0.270

AC:

1396

AN:

5176

South Asian (SAS)

AF:

0.203

AC:

978

AN:

4828

European-Finnish (FIN)

AF:

0.142

AC:

1511

AN:

10612

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.140

AC:

9528

AN:

67994

Other (OTH)

AF:

0.170

AC:

359

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1057

2114

3170

4227

5284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.117

Hom.:

436

Bravo

AF:

0.159

Asia WGS

AF:

0.219

AC:

762

AN:

3478

EpiCase

AF:

0.150

EpiControl

AF:

0.152

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neutrophil immunodeficiency syndrome

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Jan 07, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Immunodeficiency 73b with defective neutrophil chemotaxis and lymphopenia

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=274/26

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over