Variant 15-64855006-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_025201.5(PLEKHO2):c.248G>A(p.Arg83His) variant causes a missense change. The variant allele was found at a frequency of 0.000152 in 1,594,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

PLEKHO2
NM_025201.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.93

Variant links:

Genes affected

PLEKHO2 (HGNC:30026): (pleckstrin homology domain containing O2) Predicted to act upstream of or within macrophage apoptotic process. Predicted to be located in extracellular region and ficolin-1-rich granule lumen. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHO2 links:

ENSG00000249240 (HGNC:):

ENSG00000249240 links:

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=0.35237515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHO2	NM_025201.5 linkuse as main transcript	c.248G>A	p.Arg83His	missense_variant	3/6	ENST00000323544.5	NP_079477.2	Q8TD55-1
PLEKHO2	NM_001195059.2 linkuse as main transcript	c.98G>A	p.Arg33His	missense_variant	2/5		NP_001181988.1	Q8TD55-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLEKHO2	ENST00000323544.5 linkuse as main transcript	c.248G>A	p.Arg83His	missense_variant	3/6	1	NM_025201.5	ENSP00000326706.4	Q8TD55-1
PLEKHO2	ENST00000616065.4 linkuse as main transcript	c.98G>A	p.Arg33His	missense_variant	2/5	1		ENSP00000483505.1	Q8TD55-2
ENSG00000249240	ENST00000437723.1 linkuse as main transcript	c.248G>A	p.Arg83His	missense_variant	3/7	5		ENSP00000397942.1	C9J4A7
ENSG00000249240	ENST00000502574.1 linkuse as main transcript	n.382G>A		non_coding_transcript_exon_variant	3/6	2

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000831

AC:

AN:

216636

Hom.:

AF XY:

0.0000862

AC XY:

AN XY:

116006

show subpopulations

Gnomad AFR exome

AF:

0.0000724

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:

0.0000532

Gnomad NFE exome

AF:

0.000136

Gnomad OTH exome

AF:

0.000545

GnomAD4 exome

AF:

0.000158

AC:

228

AN:

1442184

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

103

AN XY:

715324

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000361

Gnomad4 FIN exome

AF:

0.0000767

Gnomad4 NFE exome

AF:

0.000194

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000814

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000578

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.248G>A (p.R83H) alteration is located in exon 3 (coding exon 3) of the PLEKHO2 gene. This alteration results from a G to A substitution at nucleotide position 248, causing the arginine (R) at amino acid position 83 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.41

.;T;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

1.0

.;L;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.9

.;N;N

REVEL

Uncertain

0.44

Sift

Benign

0.068

.;T;T

Sift4G

Benign

0.16

T;T;T

Polyphen

1.0

D;D;.

Vest4

0.40

MVP

0.71

MPC

0.56

ClinPred

0.31

GERP RS

5.2

Varity_R

0.064

gMVP

0.69

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