NM_002872.5:c.*637G>C

Variant names:

• chr22-37225405-C-G
• rs6572
• NM_002872.5:c.*637G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002872.5(RAC2):​c.*637G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,052 control chromosomes in the GnomAD database, including 17,637 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 0.46 (17636 hom., cov: 33)
  • Exomes 𝑓: 0.44 (1 hom.)
• Consequence: RAC2 NM_002872.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 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.*637G>C		3_prime_UTR	Exon 7 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.*637G>C		3_prime_UTR	Exon 7 of 7	ENSP00000249071.6
	RAC2	ENST00000699915.1		n.1274G>C		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70677 AN: 151918 Hom.: 17643 Cov.: 33

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.475

GnomAD4 exome AF: 0.438 AC: 7 AN: 16 Hom.: 1 Cov.: 0 AF XY: 0.417 AC XY: 5 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 4 AN: 8

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.465 AC: 70686 AN: 152036 Hom.: 17636 Cov.: 33 AF XY: 0.463 AC XY: 34442 AN XY: 74324

African (AFR) AF: 0.277 AC: 11499 AN: 41462

American (AMR) AF: 0.526 AC: 8035 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1775 AN: 3470

East Asian (EAS) AF: 0.518 AC: 2680 AN: 5176

South Asian (SAS) AF: 0.512 AC: 2463 AN: 4812

European-Finnish (FIN) AF: 0.499 AC: 5261 AN: 10536

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37510 AN: 67974

Other (OTH) AF: 0.471 AC: 995 AN: 2112

Alfa AF: 0.497 Hom.: 2434

Bravo AF: 0.458

Asia WGS AF: 0.501 AC: 1740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.66
PhyloP100		-0.069
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6572; hg19: chr22-37621445;