Variant chr19-39423713-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022835.3(PLEKHG2):c.2600-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,597,864 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 41 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 48 hom. )

Consequence

PLEKHG2
NM_022835.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.66

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 19-39423713-G-A is Benign according to our data. Variant chr19-39423713-G-A is described in ClinVar as [Benign]. Clinvar id is 446058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2140/152286) while in subpopulation AFR AF= 0.0483 (2005/41552). AF 95% confidence interval is 0.0465. There are 41 homozygotes in gnomad4. There are 1017 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
PLEKHG2	NM_022835.3 linkuse as main transcript	c.2600-20G>A	intron_variant	ENST00000425673.6	NP_073746.2	Q9H7P9-1
PLEKHG2	NM_001351693.2 linkuse as main transcript	c.2423-20G>A	intron_variant		NP_001338622.1
PLEKHG2	NM_001351694.2 linkuse as main transcript	c.1677+1425G>A	intron_variant		NP_001338623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHG2	ENST00000425673.6 linkuse as main transcript	c.2600-20G>A		intron_variant		2	NM_022835.3	ENSP00000392906.2		Q9H7P9-1

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2140

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00410

AC:

984

AN:

240096

Hom.:

AF XY:

0.00309

AC XY:

400

AN XY:

129244

show subpopulations

Gnomad AFR exome

AF:

0.0491

Gnomad AMR exome

AF:

0.00306

Gnomad ASJ exome

AF:

0.00494

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000710

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000267

Gnomad OTH exome

AF:

0.00206

GnomAD4 exome

AF:

0.00155

AC:

2235

AN:

1445578

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1008

AN XY:

716944

show subpopulations

Gnomad4 AFR exome

AF:

0.0468

Gnomad4 AMR exome

AF:

0.00322

Gnomad4 ASJ exome

AF:

0.00480

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000716

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000165

Gnomad4 OTH exome

AF:

0.00366

GnomAD4 genome

AF:

0.0141

AC:

2140

AN:

152286

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1017

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0483

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00587

Hom.:

Bravo

AF:

0.0158

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 21, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 19, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.015

DANN

Benign

0.51

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.

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