NM_002872.5:c.511G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002872.5(RAC2):​c.511G>C​(p.Glu171Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E171K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

RAC2
NM_002872.5 missense

Scores

5
11
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.90
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.84

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAC2NM_002872.5 linkc.511G>C p.Glu171Gln missense_variant Exon 6 of 7 ENST00000249071.11 NP_002863.1 P15153A0A024R1P2V9H0H7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAC2ENST00000249071.11 linkc.511G>C p.Glu171Gln missense_variant Exon 6 of 7 1 NM_002872.5 ENSP00000249071.6 P15153

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461060
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726852
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.82
D;D;D
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Uncertain
0.094
D
MetaRNN
Pathogenic
0.84
D;D;D
MetaSVM
Uncertain
-0.22
T
MutationAssessor
Benign
1.1
L;.;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Uncertain
-2.5
D;D;N
REVEL
Uncertain
0.53
Sift
Uncertain
0.0010
D;D;D
Sift4G
Benign
0.088
T;T;T
Polyphen
0.80
P;.;.
Vest4
0.79
MutPred
0.62
Gain of MoRF binding (P = 0.0364);.;.;
MVP
0.88
MPC
3.0
ClinPred
0.92
D
GERP RS
4.9
Varity_R
0.74
gMVP
0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-37622781; API