rs2230919

Variant names:

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.252C>T(p.Leu84Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00427 in 1,552,320 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 71 hom., cov: 31)

Exomes 𝑓: 0.0027 ( 52 hom. )

Consequence

RAC2
NM_002872.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.57

Publications

1 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=-0.57).

BP6

Variant 22-37231968-G-A is Benign according to our data. Variant chr22-37231968-G-A is described in ClinVar as Benign. ClinVar VariationId is 378454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC2	NM_002872.5 link	c.252C>T	p.Leu84Leu	synonymous_variant	Exon 4 of 7	ENST00000249071.11	NP_002863.1	P15153A0A024R1P2V9H0H7
RAC2	XM_006724286.4 link	c.252C>T	p.Leu84Leu	synonymous_variant	Exon 4 of 6		XP_006724349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000249071.11 link	c.252C>T	p.Leu84Leu	synonymous_variant	Exon 4 of 7	1	NM_002872.5	ENSP00000249071.6		P15153

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2844

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0617

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00950

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00151

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.00510

AC:

804

AN:

157696

AF XY:

0.00420

show subpopulations

Gnomad AFR exome

AF:

0.0628

Gnomad AMR exome

AF:

0.00479

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000850

Gnomad NFE exome

AF:

0.00137

Gnomad OTH exome

AF:

0.00495

GnomAD4 exome

AF:

0.00269

AC:

3763

AN:

1400178

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

1710

AN XY:

690708

show subpopulations

African (AFR)

AF:

0.0608

AC:

1923

AN:

31624

American (AMR)

AF:

0.00514

AC:

184

AN:

35806

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25184

East Asian (EAS)

AF:

0.0000559

AC:

AN:

35786

South Asian (SAS)

AF:

0.000378

AC:

AN:

79268

European-Finnish (FIN)

AF:

0.00122

AC:

AN:

49220

Middle Eastern (MID)

AF:

0.00614

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00114

AC:

1227

AN:

1079536

Other (OTH)

AF:

0.00520

AC:

302

AN:

58058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

229

458

686

915

1144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<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:

0.0188

AC:

2861

AN:

152142

Hom.:

Cov.:

AF XY:

0.0188

AC XY:

1399

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0619

AC:

2567

AN:

41480

American (AMR)

AF:

0.00948

AC:

145

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.000832

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00152

AC:

103

AN:

67986

Other (OTH)

AF:

0.0123

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

130

260

389

519

649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.00807

Hom.:

Bravo

AF:

0.0210

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jul 24, 2015

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. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2

Nov 25, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Neutrophil immunodeficiency syndrome

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.8

(source)

DANN

Benign

0.78

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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