chr22-37239015-A-G

Variant names:

• chr22-37239015-A-G
• rs2284038
• NM_002872.5:c.107+2572T>C

Variant summary

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

The NM_002872.5(RAC2):​c.107+2572T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,852 control chromosomes in the GnomAD database, including 12,696 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 0.40 (12696 hom., cov: 31)
• Consequence: RAC2 NM_002872.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 14 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAC2	NM_002872.5	c.107+2572T>C		intron_variant	Intron 2 of 6	ENST00000249071.11	NP_002863.1
RAC2	XM_006724286.4	c.107+2572T>C		intron_variant	Intron 2 of 5		XP_006724349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000249071.11	c.107+2572T>C		intron_variant	Intron 2 of 6	1	NM_002872.5	ENSP00000249071.6

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61161 AN: 151734 Hom.: 12674 Cov.: 31

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.403 AC: 61224 AN: 151852 Hom.: 12696 Cov.: 31 AF XY: 0.400 AC XY: 29704 AN XY: 74214

African (AFR) AF: 0.494 AC: 20450 AN: 41388

American (AMR) AF: 0.346 AC: 5287 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1480 AN: 3472

East Asian (EAS) AF: 0.366 AC: 1886 AN: 5146

South Asian (SAS) AF: 0.367 AC: 1764 AN: 4810

European-Finnish (FIN) AF: 0.337 AC: 3558 AN: 10552

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25588 AN: 67898

Other (OTH) AF: 0.406 AC: 856 AN: 2108

Alfa AF: 0.382 Hom.: 48218

Bravo AF: 0.406

Asia WGS AF: 0.386 AC: 1342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.81
PhyloP100		-0.15
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: rs2284038; hg19: chr22-37635055;