Variant 19-39414128-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_022835.3(PLEKHG2):c.42C>G(p.Ser14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000436 in 1,551,604 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 13 hom. )

Consequence

PLEKHG2
NM_022835.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.29

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]

PLEKHG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 19-39414128-C-G is Benign according to our data. Variant chr19-39414128-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 722233.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHG2	NM_022835.3 linkuse as main transcript	c.42C>G	p.Ser14Arg	missense_variant	2/19	ENST00000425673.6	NP_073746.2	Q9H7P9-1
PLEKHG2	NM_001351693.2 linkuse as main transcript	c.42C>G	p.Ser14Arg	missense_variant	2/20		NP_001338622.1
PLEKHG2	NM_001351694.2 linkuse as main transcript	c.42C>G	p.Ser14Arg	missense_variant	2/18		NP_001338623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHG2	ENST00000425673.6 linkuse as main transcript	c.42C>G	p.Ser14Arg	missense_variant	2/19	2	NM_022835.3	ENSP00000392906.2		Q9H7P9-1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00786

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00106

AC:

165

AN:

155820

Hom.:

AF XY:

0.00152

AC XY:

126

AN XY:

82630

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:

0.00716

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000166

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.000457

AC:

640

AN:

1399244

Hom.:

Cov.:

AF XY:

0.000674

AC XY:

465

AN XY:

690152

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:

0.00771

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000236

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00745

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000279

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.00205

AC:

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0050

T;.;.;.;.;.

Eigen

Benign

0.098

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.85

T;T;T;T;T;T

MetaRNN

Benign

0.0056

T;T;T;T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.0

M;.;.;.;M;.

MutationTaster

Benign

0.99

N;N;N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.7

N;.;N;N;N;N

REVEL

Benign

0.065

Sift

Uncertain

0.0010

D;.;D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;D;D

Polyphen

0.98

D;.;B;.;P;.

Vest4

0.20

MutPred

0.21

Loss of ubiquitination at K12 (P = 0.0116);Loss of ubiquitination at K12 (P = 0.0116);Loss of ubiquitination at K12 (P = 0.0116);Loss of ubiquitination at K12 (P = 0.0116);Loss of ubiquitination at K12 (P = 0.0116);Loss of ubiquitination at K12 (P = 0.0116);

MVP

0.82

ClinPred

0.15

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.20

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: 0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over