rs12166968

Positions:

• chr22-37225318-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.*724G>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 0.0641 in 152,204 control chromosomes in the GnomAD database, including 394 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 0.064 (394 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAC2 NM_002872.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354

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=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC2	NM_002872.5	c.*724G>C		3_prime_UTR_variant	7/7	ENST00000249071.11	NP_002863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000249071.11	c.*724G>C		3_prime_UTR_variant	7/7	1	NM_002872.5	ENSP00000249071	P1
RAC2	ENST00000699915.1	n.1361G>C		non_coding_transcript_exon_variant	7/7

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9742 AN: 152086 Hom.: 394 Cov.: 33

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0963

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0596

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0605

Gnomad OTH AF: 0.0665

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0641 AC: 9750 AN: 152204 Hom.: 394 Cov.: 33 AF XY: 0.0657 AC XY: 4889 AN XY: 74422

Gnomad4 AFR AF: 0.0427

Gnomad4 AMR AF: 0.0967

Gnomad4 ASJ AF: 0.0839

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0596

Gnomad4 NFE AF: 0.0605

Gnomad4 OTH AF: 0.0658

Alfa AF: 0.0649 Hom.: 50

Bravo AF: 0.0647

Asia WGS AF: 0.120 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.8
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs12166968; hg19: chr22-37621358;