rs1064498

Variant names:

• chr22-37226775-A-G
• rs1064498
• NM_002872.5:c.477T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-37226775-A-G
• chr22-37226775-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.935
• Publications: 16 publications found

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)

ACMG classification

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002872.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC2	NM_002872.5	MANE Select	c.477T>C	p.Ala159Ala	synonymous	Exon 6 of 7	NP_002863.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC2	ENST00000249071.11	TSL:1 MANE Select	c.477T>C	p.Ala159Ala	synonymous	Exon 6 of 7	ENSP00000249071.6
	RAC2	ENST00000481215.1	TSL:1	n.302T>C		non_coding_transcript_exon	Exon 2 of 3
	RAC2	ENST00000405484.5	TSL:3	c.456T>C	p.Ala152Ala	synonymous	Exon 6 of 6	ENSP00000385590.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33043 AN: 151414 Hom.: 4554 Cov.: 31

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

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.: 33 AF XY: 0.148 AC XY: 107765 AN XY: 726634

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

GnomAD4 genome AF: 0.218 AC: 33092 AN: 151532 Hom.: 4567 Cov.: 31 AF XY: 0.216 AC XY: 16007 AN XY: 74048

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: 75 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9802 AN: 67860

Other (OTH) AF: 0.213 AC: 449 AN: 2108

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Neutrophil immunodeficiency syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.7
DANN	Benign	0.65
PhyloP100		-0.94
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1064498; hg19: chr22-37622815; COSMIC: COSV50773917;