22-37228959-A-G

Position:

• chr22-37228959-A-G

Variant summary

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

The NM_002872.5(RAC2):​c.449-2156T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,060 control chromosomes in the GnomAD database, including 16,099 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 0.45 (16099 hom., cov: 33)
• Consequence: RAC2 NM_002872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC2	NM_002872.5	c.449-2156T>C		intron_variant		ENST00000249071.11	NP_002863.1
RAC2	XM_006724286.4	c.449-1016T>C		intron_variant			XP_006724349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000249071.11	c.449-2156T>C		intron_variant		1	NM_002872.5	ENSP00000249071.6

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68563 AN: 151942 Hom.: 16062 Cov.: 33

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.452

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.451 AC: 68654 AN: 152060 Hom.: 16099 Cov.: 33 AF XY: 0.446 AC XY: 33141 AN XY: 74316

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.453

Alfa AF: 0.412 Hom.: 6235

Bravo AF: 0.459

Asia WGS AF: 0.408 AC: 1418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.0
DANN	Benign	0.89

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: rs739041; hg19: chr22-37624999; COSMIC: COSV50774760; COSMIC: COSV50774760;