dbSNP rs9607432: RAC2:c.108-1525A>G (chr22-37234443-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002872.5(RAC2):c.108-1525A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,178 control chromosomes in the GnomAD database, including 1,012 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 0.11 ( 1012 hom., cov: 32)

Consequence

RAC2
NM_002872.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.59

Publications

7 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC2	NM_002872.5 link	c.108-1525A>G		intron_variant	Intron 2 of 6	ENST00000249071.11	NP_002863.1
RAC2	XM_006724286.4 link	c.108-1525A>G		intron_variant	Intron 2 of 5		XP_006724349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000249071.11 link	c.108-1525A>G		intron_variant	Intron 2 of 6	1	NM_002872.5	ENSP00000249071.6

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16699

AN:

152058

Hom.:

1009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0975

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0799

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.124

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

GnomAD4 genome

AF:

0.110

AC:

16713

AN:

152178

Hom.:

1012

Cov.:

AF XY:

0.110

AC XY:

8195

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0974

AC:

4046

AN:

41532

American (AMR)

AF:

0.0799

AC:

1221

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

619

AN:

3472

East Asian (EAS)

AF:

0.257

AC:

1328

AN:

5166

South Asian (SAS)

AF:

0.110

AC:

529

AN:

4828

European-Finnish (FIN)

AF:

0.102

AC:

1086

AN:

10600

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.110

AC:

7486

AN:

67976

Other (OTH)

AF:

0.124

AC:

262

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

756

1513

2269

3026

3782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

186

372

558

744

930

<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:

0.112

Hom.:

164

Bravo

AF:

0.108

Asia WGS

AF:

0.169

AC:

587

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.55

(source)

DANN

Benign

0.50

PhyloP100

-1.6

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over