Genetic Variant NM_025201.5:c.232C>T (chr15-64854990-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_025201.5(PLEKHO2):c.232C>T(p.Leu78Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,388 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PLEKHO2
NM_025201.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26671624).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025201.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHO2	NM_025201.5	MANE Select	c.232C>T	p.Leu78Phe	missense	Exon 3 of 6	NP_079477.2
	PLEKHO2	NM_001195059.2		c.82C>T	p.Leu28Phe	missense	Exon 2 of 5	NP_001181988.1	Q8TD55-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLEKHO2	ENST00000323544.5	TSL:1 MANE Select	c.232C>T	p.Leu78Phe	missense	Exon 3 of 6	ENSP00000326706.4	Q8TD55-1
PLEKHO2	ENST00000616065.4	TSL:1	c.82C>T	p.Leu28Phe	missense	Exon 2 of 5	ENSP00000483505.1	Q8TD55-2
ENSG00000249240	ENST00000437723.1	TSL:5	c.232C>T	p.Leu78Phe	missense	Exon 3 of 7	ENSP00000397942.1	C9J4A7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000850

AC:

AN:

235320

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1453388

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722012

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.00

AC:

AN:

43224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25870

East Asian (EAS)

AF:

0.00

AC:

AN:

39542

South Asian (SAS)

AF:

0.00

AC:

AN:

84342

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52918

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1108130

Other (OTH)

AF:

0.00

AC:

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.82

M_CAP

Benign

0.028

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.58

PhyloP100

1.5

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.69

REVEL

Uncertain

0.37

Sift

Benign

0.092

Sift4G

Benign

0.14

Polyphen

1.0

Vest4

0.40

MutPred

0.40

Gain of methylation at K79 (P = 0.0441)

MVP

0.61

MPC

0.19

ClinPred

0.36

GERP RS

4.1

Varity_R

0.060

gMVP

0.16

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over