22-37248075-T-C

Variant names:

• chr22-37248075-T-C
• rs6000632
• ENST00000699915.1:n.94-6417A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000699915.1(RAC2):​n.94-6417A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,074 control chromosomes in the GnomAD database, including 46,475 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 0.78 (46475 hom., cov: 31)
• Consequence: RAC2 ENST00000699915.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.624
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 73b with defective neutrophil chemotaxis and lymphopenia

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen
• neutrophil immunodeficiency syndrome

  Inheritance: AD, Unknown Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000699915.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC2	ENST00000699915.1		n.94-6417A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118189 AN: 151956 Hom.: 46408 Cov.: 31

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.778 AC: 118323 AN: 152074 Hom.: 46475 Cov.: 31 AF XY: 0.775 AC XY: 57612 AN XY: 74324

African (AFR) AF: 0.875 AC: 36304 AN: 41492

American (AMR) AF: 0.756 AC: 11555 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2722 AN: 3468

East Asian (EAS) AF: 0.605 AC: 3130 AN: 5174

South Asian (SAS) AF: 0.791 AC: 3799 AN: 4800

European-Finnish (FIN) AF: 0.711 AC: 7519 AN: 10582

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50655 AN: 67966

Other (OTH) AF: 0.783 AC: 1652 AN: 2110

Alfa AF: 0.763 Hom.: 57957

Bravo AF: 0.784

Asia WGS AF: 0.710 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.92
DANN	Benign	0.68
PhyloP100		-0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6000632; hg19: chr22-37644115;