19-39415058-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022835.3(PLEKHG2):ā€‹c.176G>Cā€‹(p.Gly59Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000347 in 1,441,340 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes š‘“: 0.0000035 ( 0 hom. )

Consequence

PLEKHG2
NM_022835.3 missense

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.57
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28374282).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLEKHG2NM_022835.3 linkc.176G>C p.Gly59Ala missense_variant Exon 3 of 19 ENST00000425673.6 NP_073746.2 Q9H7P9-1
PLEKHG2NM_001351694.2 linkc.176G>C p.Gly59Ala missense_variant Exon 3 of 18 NP_001338623.1
PLEKHG2NM_001351693.2 linkc.110-111G>C intron_variant Intron 2 of 19 NP_001338622.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLEKHG2ENST00000425673.6 linkc.176G>C p.Gly59Ala missense_variant Exon 3 of 19 2 NM_022835.3 ENSP00000392906.2 Q9H7P9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000481
AC:
1
AN:
207826
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
113330
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000112
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000347
AC:
5
AN:
1441340
Hom.:
0
Cov.:
31
AF XY:
0.00000140
AC XY:
1
AN XY:
715432
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:
0.00000453
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Uncertain
0.012
T
BayesDel_noAF
Benign
-0.22
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0058
T;.;.;.
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.80
T;D;T;D
M_CAP
Benign
0.082
D
MetaRNN
Benign
0.28
T;T;T;T
MetaSVM
Benign
-0.44
T
MutationAssessor
Uncertain
2.0
M;.;M;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-1.4
N;N;N;N
REVEL
Benign
0.14
Sift
Uncertain
0.0010
D;D;D;T
Sift4G
Uncertain
0.051
T;D;T;T
Polyphen
1.0
D;.;D;.
Vest4
0.48
MutPred
0.20
Gain of relative solvent accessibility (P = 0.09);.;Gain of relative solvent accessibility (P = 0.09);.;
MVP
0.79
ClinPred
0.85
D
GERP RS
5.0
Varity_R
0.25
gMVP
0.46

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1352059198; hg19: chr19-39905698; API