rs1064498

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.477T>C(p.Ala159Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,612,120 control chromosomes in the GnomAD database, including 22,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4567 hom., cov: 31)

Exomes 𝑓: 0.15 ( 18370 hom. )

Consequence

RAC2
NM_002872.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.935

Publications

16 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=-0.74).

BP6

Variant 22-37226775-A-G is Benign according to our data. Variant chr22-37226775-A-G is described in ClinVar as [Benign]. Clinvar id is 138864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.935 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC2	NM_002872.5 link	c.477T>C	p.Ala159Ala	synonymous_variant	Exon 6 of 7	ENST00000249071.11	NP_002863.1	P15153A0A024R1P2V9H0H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000249071.11 link	c.477T>C	p.Ala159Ala	synonymous_variant	Exon 6 of 7	1	NM_002872.5	ENSP00000249071.6		P15153

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33043

AN:

151414

Hom.:

4554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.293

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.212

GnomAD2 exomes

AF:

0.164

AC:

41061

AN:

250422

AF XY:

0.159

show subpopulations

Gnomad AFR exome

AF:

0.403

Gnomad AMR exome

AF:

0.0912

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.150

AC:

219192

AN:

1460588

Hom.:

18370

Cov.:

AF XY:

0.148

AC XY:

107765

AN XY:

726634

show subpopulations

African (AFR)

AF:

0.397

AC:

13289

AN:

33450

American (AMR)

AF:

0.0992

AC:

4432

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

5202

AN:

26100

East Asian (EAS)

AF:

0.285

AC:

11327

AN:

39690

South Asian (SAS)

AF:

0.105

AC:

9016

AN:

86250

European-Finnish (FIN)

AF:

0.148

AC:

7839

AN:

53074

Middle Eastern (MID)

AF:

0.197

AC:

1136

AN:

5762

European-Non Finnish (NFE)

AF:

0.141

AC:

156150

AN:

1111282

Other (OTH)

AF:

0.179

AC:

10801

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

10602

21204

31806

42408

53010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.218

AC:

33092

AN:

151532

Hom.:

4567

Cov.:

AF XY:

0.216

AC XY:

16007

AN XY:

74048

show subpopulations

African (AFR)

AF:

0.394

AC:

16230

AN:

41156

American (AMR)

AF:

0.132

AC:

2021

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

700

AN:

3468

East Asian (EAS)

AF:

0.292

AC:

1502

AN:

5138

South Asian (SAS)

AF:

0.122

AC:

585

AN:

4812

European-Finnish (FIN)

AF:

0.150

AC:

1585

AN:

10532

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.144

AC:

9802

AN:

67860

Other (OTH)

AF:

0.213

AC:

449

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1227

2454

3681

4908

6135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.156

Hom.:

1560

Bravo

AF:

0.227

Asia WGS

AF:

0.219

AC:

760

AN:

3478

EpiCase

AF:

0.150

EpiControl

AF:

0.153

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 -

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. -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 21% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Neutrophil immunodeficiency syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.74

CADD

Benign

8.7

(source)

DANN

Benign

0.65

PhyloP100

-0.94

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1064498

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