22-37242920-T-C

Position:

• chr22-37242920-T-C

Variant summary

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

The NM_002872.5(RAC2):​c.35+1194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,176 control chromosomes in the GnomAD database, including 26,261 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 0.58 (26261 hom., cov: 34)
• Consequence: RAC2 NM_002872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC2	NM_002872.5	c.35+1194A>G		intron_variant		ENST00000249071.11	NP_002863.1
RAC2	XM_006724286.4	c.35+1194A>G		intron_variant			XP_006724349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000249071.11	c.35+1194A>G		intron_variant		1	NM_002872.5	ENSP00000249071	P1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88896 AN: 152058 Hom.: 26221 Cov.: 34

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.585 AC: 88996 AN: 152176 Hom.: 26261 Cov.: 34 AF XY: 0.579 AC XY: 43066 AN XY: 74400

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.590

Alfa AF: 0.564 Hom.: 44919

Bravo AF: 0.593

Asia WGS AF: 0.622 AC: 2160 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	6.5
DANN	Benign	0.77

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: rs2213430; hg19: chr22-37638960;