22-37226707-G-C

Position:

• chr22-37226707-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002872.5(RAC2):​c.545C>G​(p.Thr182Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAC2 NM_002872.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.86

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17681086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAC2	NM_002872.5	c.545C>G	p.Thr182Arg	missense_variant	6/7	ENST00000249071.11	NP_002863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAC2	ENST00000249071.11	c.545C>G	p.Thr182Arg	missense_variant	6/7	1	NM_002872.5	ENSP00000249071.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249900 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135408

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000189

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.32	T;T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.22	N;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.87	N;N;N
REVEL	Benign	0.23
Sift	Benign	0.55	T;T;T
Sift4G	Benign	0.42	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.41
MutPred		0.38		Gain of MoRF binding (P = 0.0146);.;.;
MVP		0.75
MPC		0.078
ClinPred		0.20	T
GERP RS		3.9
Varity_R		0.036
gMVP		0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs141308774; hg19: chr22-37622747;