rs8135343

Positions:

• chr22-37231805-G-A
• chr22-37231805-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000249071.11(RAC2):​c.288+127C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,117,006 control chromosomes in the GnomAD database, including 78,788 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 0.38 (11402 hom., cov: 30)
  • Exomes 𝑓: 0.37 (67386 hom.)
• Consequence: RAC2 ENST00000249071.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC2	NM_002872.5	c.288+127C>T		intron_variant		ENST00000249071.11	NP_002863.1
RAC2	XM_006724286.4	c.288+127C>T		intron_variant			XP_006724349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000249071.11	c.288+127C>T		intron_variant		1	NM_002872.5	ENSP00000249071	P1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58290 AN: 151488 Hom.: 11374 Cov.: 30

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.388

GnomAD4 exome AF: 0.370 AC: 357451 AN: 965400 Hom.: 67386 AF XY: 0.368 AC XY: 180160 AN XY: 489924

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.326

Gnomad4 ASJ exome AF: 0.437

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.322

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.386

GnomAD4 genome AF: 0.385 AC: 58356 AN: 151606 Hom.: 11402 Cov.: 30 AF XY: 0.380 AC XY: 28171 AN XY: 74066

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.385

Alfa AF: 0.375 Hom.: 1701

Bravo AF: 0.389

Asia WGS AF: 0.323 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.4
DANN	Benign	0.80

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: rs8135343; hg19: chr22-37627845;