ENST00000699915.1:n.93+6272T>C

Variant names:

• chr22-37253230-A-G
• rs12484031
• ENST00000699915.1:n.93+6272T>C

Variant summary

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

The ENST00000699915.1(RAC2):​n.93+6272T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,102 control chromosomes in the GnomAD database, including 825 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 0.10 (825 hom., cov: 32)
• Consequence: RAC2 ENST00000699915.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 7 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
• immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia

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

  Inheritance: Unknown, AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

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 (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000699915.1	n.93+6272T>C		intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15351 AN: 151984 Hom.: 824 Cov.: 32

Gnomad AFR AF: 0.0792

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0873

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0984

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.101 AC: 15357 AN: 152102 Hom.: 825 Cov.: 32 AF XY: 0.103 AC XY: 7676 AN XY: 74366

African (AFR) AF: 0.0791 AC: 3280 AN: 41472

American (AMR) AF: 0.133 AC: 2024 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 388 AN: 3472

East Asian (EAS) AF: 0.0875 AC: 454 AN: 5186

South Asian (SAS) AF: 0.198 AC: 954 AN: 4810

European-Finnish (FIN) AF: 0.0984 AC: 1041 AN: 10582

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6897 AN: 67998

Other (OTH) AF: 0.0986 AC: 208 AN: 2110

Alfa AF: 0.0991 Hom.: 908

Bravo AF: 0.0993

Asia WGS AF: 0.139 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.72
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs12484031; hg19: chr22-37649270;