22-37242920-T-C

Variant names:

• chr22-37242920-T-C
• rs2213430
• NM_002872.5:c.35+1194A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002872.5. 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
	RAC2	NM_002872.5	MANE Select	c.35+1194A>G		intron	N/A	NP_002863.1	P15153

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC2	ENST00000249071.11	TSL:1 MANE Select	c.35+1194A>G		intron	N/A	ENSP00000249071.6	P15153
	RAC2	ENST00000870381.1		c.35+1194A>G		intron	N/A	ENSP00000540440.1
	RAC2	ENST00000870383.1		c.35+1194A>G		intron	N/A	ENSP00000540442.1

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

African (AFR) AF: 0.658 AC: 27312 AN: 41524

American (AMR) AF: 0.576 AC: 8819 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1898 AN: 3472

East Asian (EAS) AF: 0.601 AC: 3112 AN: 5174

South Asian (SAS) AF: 0.637 AC: 3072 AN: 4822

European-Finnish (FIN) AF: 0.468 AC: 4956 AN: 10584

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38049 AN: 67986

Other (OTH) AF: 0.590 AC: 1244 AN: 2110

Alfa AF: 0.568 Hom.: 91042

Bravo AF: 0.593

Asia WGS AF: 0.622 AC: 2160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.77
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2213430; hg19: chr22-37638960;