rs767871729

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022835.3(PLEKHG2):​c.58G>A​(p.Gly20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

PLEKHG2
NM_022835.3 missense

Scores

1
3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.581
Variant links:
Genes affected
PLEKHG2 (HGNC:29515): (pleckstrin homology and RhoGEF domain containing G2) The protein encoded by this gene is a RhoGTPase that can activate CDC42 by promoting exchange of GDP for GTP on CDC42. The encoded protein is activated by binding to the beta and gamma subunits of heterotrimeric guanine nucleotide-binding protein. Defects in this gene have been associated with leukodystrophy and acquired microcephaly with or without dystonia. [provided by RefSeq, May 2017]

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ACMG classification

Classification made for transcript

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=0.097653866).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLEKHG2NM_022835.3 linkc.58G>A p.Gly20Ser missense_variant Exon 2 of 19 ENST00000425673.6 NP_073746.2 Q9H7P9-1
PLEKHG2NM_001351693.2 linkc.58G>A p.Gly20Ser missense_variant Exon 2 of 20 NP_001338622.1
PLEKHG2NM_001351694.2 linkc.58G>A p.Gly20Ser missense_variant Exon 2 of 18 NP_001338623.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLEKHG2ENST00000425673.6 linkc.58G>A p.Gly20Ser missense_variant Exon 2 of 19 2 NM_022835.3 ENSP00000392906.2 Q9H7P9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1399180
Hom.:
0
Cov.:
30
AF XY:
0.00000145
AC XY:
1
AN XY:
690122
show subpopulations
Gnomad4 AFR exome
AF:
0.0000316
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:
0.00
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
Benign
0.080
BayesDel_addAF
Benign
-0.078
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0014
T;.;.;.;.;.
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.053
N
LIST_S2
Benign
0.77
T;D;T;T;T;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.098
T;T;T;T;T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
1.0
L;.;.;.;L;.
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.12
N;.;N;N;N;N
REVEL
Benign
0.11
Sift
Pathogenic
0.0
D;.;T;D;D;D
Sift4G
Benign
0.18
T;D;T;T;T;T
Polyphen
0.94
P;.;B;.;P;.
Vest4
0.12
MutPred
0.17
Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);
MVP
0.57
ClinPred
0.41
T
GERP RS
-1.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.19

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr19-39904784; API