Variant 15-64865330-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025201.5(PLEKHO2):c.915G>C(p.Glu305Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 1,613,906 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000033 ( 1 hom. )

Consequence

PLEKHO2
NM_025201.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011502415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHO2	NM_025201.5 linkuse as main transcript	c.915G>C	p.Glu305Asp	missense_variant	6/6	ENST00000323544.5
PLEKHO2	NM_001195059.2 linkuse as main transcript	c.765G>C	p.Glu255Asp	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHO2	ENST00000323544.5 linkuse as main transcript	c.915G>C	p.Glu305Asp	missense_variant	6/6	1	NM_025201.5	P1	Q8TD55-1
PLEKHO2	ENST00000616065.4 linkuse as main transcript	c.765G>C	p.Glu255Asp	missense_variant	5/5	1			Q8TD55-2

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000918

AC:

AN:

250594

Hom.:

AF XY:

0.0000811

AC XY:

AN XY:

135554

show subpopulations

Gnomad AFR exome

AF:

0.00136

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:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1461608

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000368

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000630

Hom.:

Bravo

AF:

0.000438

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

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

Apr 23, 2024

The c.915G>C (p.E305D) alteration is located in exon 6 (coding exon 6) of the PLEKHO2 gene. This alteration results from a G to C substitution at nucleotide position 915, causing the glutamic acid (E) at amino acid position 305 to be replaced by an aspartic acid (D). 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

Benign

0.11

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.50

PrimateAI

Benign

0.38

Sift4G

Benign

0.26

T;T

Polyphen

0.084

B;B

Vest4

0.24

MutPred

0.27

.;Loss of glycosylation at P309 (P = 0.1773);

MVP

0.42

MPC

0.25

ClinPred

0.033

GERP RS

3.9

Varity_R

0.089

gMVP

0.064

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