dbSNP rs5756573: RAC2:c.107+3852C>T (chr22-37237735-G-A) – 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.107+3852C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,070 control chromosomes in the GnomAD database, including 2,134 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 0.14 ( 2134 hom., cov: 31)

Consequence

RAC2
NM_002872.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.166

Publications

9 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC2	NM_002872.5 link	c.107+3852C>T		intron_variant	Intron 2 of 6	ENST00000249071.11	NP_002863.1	P15153A0A024R1P2V9H0H7
RAC2	XM_006724286.4 link	c.107+3852C>T		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.107+3852C>T		intron_variant	Intron 2 of 6	1	NM_002872.5	ENSP00000249071.6		P15153

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22040

AN:

151952

Hom.:

2139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0302

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.360

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.146

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

GnomAD4 genome

AF:

0.145

AC:

22027

AN:

152070

Hom.:

2134

Cov.:

AF XY:

0.153

AC XY:

11368

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.0301

AC:

1249

AN:

41532

American (AMR)

AF:

0.207

AC:

3164

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

679

AN:

3472

East Asian (EAS)

AF:

0.360

AC:

1850

AN:

5142

South Asian (SAS)

AF:

0.215

AC:

1035

AN:

4810

European-Finnish (FIN)

AF:

0.247

AC:

2606

AN:

10564

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.162

AC:

10999

AN:

67946

Other (OTH)

AF:

0.145

AC:

306

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

889

1778

2666

3555

4444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.155

Hom.:

3856

Bravo

AF:

0.137

Asia WGS

AF:

0.274

AC:

951

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.0

(source)

DANN

Benign

0.79

PhyloP100

-0.17

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