19-39415020-C-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_022835.3(PLEKHG2):ā€‹c.138C>Gā€‹(p.Pro46Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000472 in 1,597,982 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.00053 ( 0 hom., cov: 32)
Exomes š‘“: 0.00047 ( 4 hom. )

Consequence

PLEKHG2
NM_022835.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.19
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 Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 19-39415020-C-G is Benign according to our data. Variant chr19-39415020-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 725696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.19 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLEKHG2NM_022835.3 linkc.138C>G p.Pro46Pro synonymous_variant Exon 3 of 19 ENST00000425673.6 NP_073746.2 Q9H7P9-1
PLEKHG2NM_001351694.2 linkc.138C>G p.Pro46Pro synonymous_variant Exon 3 of 18 NP_001338623.1
PLEKHG2NM_001351693.2 linkc.110-149C>G 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.138C>G p.Pro46Pro synonymous_variant Exon 3 of 19 2 NM_022835.3 ENSP00000392906.2 Q9H7P9-1

Frequencies

GnomAD3 genomes
AF:
0.000526
AC:
80
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0150
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00114
AC:
257
AN:
225664
Hom.:
2
AF XY:
0.00112
AC XY:
139
AN XY:
123564
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0145
Gnomad SAS exome
AF:
0.000141
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000202
Gnomad OTH exome
AF:
0.000177
GnomAD4 exome
AF:
0.000466
AC:
674
AN:
1445652
Hom.:
4
Cov.:
31
AF XY:
0.000463
AC XY:
332
AN XY:
717096
show subpopulations
Gnomad4 AFR exome
AF:
0.0000303
Gnomad4 AMR exome
AF:
0.0000229
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0160
Gnomad4 SAS exome
AF:
0.000201
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000136
Gnomad4 OTH exome
AF:
0.000268
GnomAD4 genome
AF:
0.000525
AC:
80
AN:
152330
Hom.:
0
Cov.:
32
AF XY:
0.000564
AC XY:
42
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0150
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000223
Hom.:
0
Bravo
AF:
0.000676
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Feb 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

PLEKHG2: BP4, BP7, BS1 -

Dec 09, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.27
DANN
Benign
0.63
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs144626871; hg19: chr19-39905660; API