22-37233898-A-C

Variant names:

• chr22-37233898-A-C
• rs9607431
• NM_002872.5:c.108-980T>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.108-980T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,122 control chromosomes in the GnomAD database, including 1,474 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 0.13 (1474 hom., cov: 32)
• Consequence: RAC2 NM_002872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC2	NM_002872.5	MANE Select	c.108-980T>G		intron	N/A	NP_002863.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAC2	ENST00000249071.11	TSL:1 MANE Select	c.108-980T>G		intron	N/A	ENSP00000249071.6
	RAC2	ENST00000405484.5	TSL:3	c.87-980T>G		intron	N/A	ENSP00000385590.1
	RAC2	ENST00000441619.5	TSL:5	c.108-980T>G		intron	N/A	ENSP00000403778.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20412 AN: 152000 Hom.: 1468 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.134 AC: 20436 AN: 152122 Hom.: 1474 Cov.: 32 AF XY: 0.135 AC XY: 10007 AN XY: 74366

African (AFR) AF: 0.161 AC: 6667 AN: 41496

American (AMR) AF: 0.0917 AC: 1402 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 618 AN: 3466

East Asian (EAS) AF: 0.258 AC: 1333 AN: 5164

South Asian (SAS) AF: 0.160 AC: 775 AN: 4830

European-Finnish (FIN) AF: 0.111 AC: 1174 AN: 10600

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8019 AN: 67960

Other (OTH) AF: 0.146 AC: 309 AN: 2112

Alfa AF: 0.119 Hom.: 1514

Bravo AF: 0.134

Asia WGS AF: 0.206 AC: 718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.7
DANN	Benign	0.74
PhyloP100		1.8
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: rs9607431; hg19: chr22-37629938;