22-37236730-T-G

Variant names:

• chr22-37236730-T-G
• rs13058338
• NM_002872.5:c.108-3812A>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002872.5(RAC2):​c.108-3812A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00511 in 151,970 control chromosomes in the GnomAD database, including 2 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 0.0051 (2 hom., cov: 32)
• Consequence: RAC2 NM_002872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 58 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High Homozygotes in GnomAd4 at 2 AR,AD,Unknown gene

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.108-3812A>C		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.108-3812A>C		intron	N/A	ENSP00000249071.6
	RAC2	ENST00000405484.5	TSL:3	c.87-3812A>C		intron	N/A	ENSP00000385590.1
	RAC2	ENST00000441619.5	TSL:5	c.108-3812A>C		intron	N/A	ENSP00000403778.1

Frequencies

GnomAD3 genomes AF: 0.00514 AC: 781 AN: 151850 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00897

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00353

Gnomad FIN AF: 0.000285

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00638

Gnomad OTH AF: 0.00912

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

GnomAD4 genome AF: 0.00511 AC: 777 AN: 151970 Hom.: 2 Cov.: 32 AF XY: 0.00471 AC XY: 350 AN XY: 74280

African (AFR) AF: 0.00133 AC: 55 AN: 41454

American (AMR) AF: 0.00896 AC: 137 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0303 AC: 105 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00312 AC: 15 AN: 4814

European-Finnish (FIN) AF: 0.000285 AC: 3 AN: 10518

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00639 AC: 434 AN: 67966

Other (OTH) AF: 0.00901 AC: 19 AN: 2108

Alfa AF: 0.000763 Hom.: 205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.79
PhyloP100		-0.23

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: rs13058338; hg19: chr22-37632770;