rs6572

chr22-37225405-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAC2	NM_002872.5	c.*637G>C		3_prime_UTR_variant	7/7	ENST00000249071.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAC2	ENST00000249071.11	c.*637G>C		3_prime_UTR_variant	7/7	1	NM_002872.5	P1
RAC2	ENST00000699915.1	n.1274G>C		non_coding_transcript_exon_variant	7/7

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

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.333

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

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.471

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.4
Dann	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs6572; hg19: chr22-37621445;