19-39415058-G-C
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_022835.3(PLEKHG2):āc.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
NM_022835.3 missense
Scores
1
9
9
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.57
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 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 |
---|---|---|---|---|---|---|---|---|
PLEKHG2 | NM_022835.3 | c.176G>C | p.Gly59Ala | missense_variant | Exon 3 of 19 | ENST00000425673.6 | NP_073746.2 | |
PLEKHG2 | NM_001351694.2 | c.176G>C | p.Gly59Ala | missense_variant | Exon 3 of 18 | NP_001338623.1 | ||
PLEKHG2 | NM_001351693.2 | c.110-111G>C | intron_variant | Intron 2 of 19 | NP_001338622.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000481 AC: 1AN: 207826Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 113330
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GnomAD4 exome AF: 0.00000347 AC: 5AN: 1441340Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1AN XY: 715432
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GnomAD4 genome Cov.: 32
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32
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;D;T;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;.
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;T
Sift4G
Uncertain
T;D;T;T
Polyphen
D;.;D;.
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.09);.;Gain of relative solvent accessibility (P = 0.09);.;
MVP
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at