dbSNP rs12595292: PLEKHO2:p.Lys133Lys (chr15-64861491-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_025201.5(PLEKHO2):c.399G>A(p.Lys133Lys) variant causes a synonymous change. The variant allele was found at a frequency of 0.171 in 1,600,830 control chromosomes in the GnomAD database, including 33,767 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 3410 hom., cov: 32)

Exomes 𝑓: 0.17 ( 30357 hom. )

Consequence

PLEKHO2
NM_025201.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.16

Publications

27 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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHO2	NM_025201.5 link	c.399G>A	p.Lys133Lys	synonymous_variant	Exon 5 of 6	ENST00000323544.5	NP_079477.2	Q8TD55-1
PLEKHO2	NM_001195059.2 link	c.249G>A	p.Lys83Lys	synonymous_variant	Exon 4 of 5		NP_001181988.1	Q8TD55-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLEKHO2	ENST00000323544.5 link	c.399G>A	p.Lys133Lys	synonymous_variant	Exon 5 of 6	1	NM_025201.5	ENSP00000326706.4	Q8TD55-1
PLEKHO2	ENST00000616065.4 link	c.249G>A	p.Lys83Lys	synonymous_variant	Exon 4 of 5	1		ENSP00000483505.1	Q8TD55-2
ENSG00000249240	ENST00000437723.1 link	c.399G>A	p.Lys133Lys	synonymous_variant	Exon 5 of 7	5		ENSP00000397942.1	C9J4A7
ENSG00000249240	ENST00000502574.1 link	n.533G>A		non_coding_transcript_exon_variant	Exon 5 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26794

AN:

152122

Hom.:

3404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.749

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.189

GnomAD2 exomes

AF:

0.223

AC:

50695

AN:

227122

AF XY:

0.215

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.332

Gnomad ASJ exome

AF:

0.178

Gnomad EAS exome

AF:

0.751

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.171

AC:

247495

AN:

1448590

Hom.:

30357

Cov.:

AF XY:

0.171

AC XY:

122910

AN XY:

719628

show subpopulations

African (AFR)

AF:

0.114

AC:

3812

AN:

33316

American (AMR)

AF:

0.321

AC:

13532

AN:

42148

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

4646

AN:

25738

East Asian (EAS)

AF:

0.790

AC:

30787

AN:

38986

South Asian (SAS)

AF:

0.172

AC:

14444

AN:

83896

European-Finnish (FIN)

AF:

0.197

AC:

10269

AN:

52188

Middle Eastern (MID)

AF:

0.197

AC:

1123

AN:

5702

European-Non Finnish (NFE)

AF:

0.142

AC:

157510

AN:

1106748

Other (OTH)

AF:

0.190

AC:

11372

AN:

59868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

8233

16466

24698

32931

41164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5896

11792

17688

23584

29480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.176

AC:

26816

AN:

152240

Hom.:

3410

Cov.:

AF XY:

0.182

AC XY:

13532

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.119

AC:

4937

AN:

41560

American (AMR)

AF:

0.242

AC:

3707

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

628

AN:

3464

East Asian (EAS)

AF:

0.749

AC:

3860

AN:

5156

South Asian (SAS)

AF:

0.178

AC:

860

AN:

4828

European-Finnish (FIN)

AF:

0.204

AC:

2165

AN:

10600

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.149

AC:

10147

AN:

68014

Other (OTH)

AF:

0.195

AC:

411

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1037

2075

3112

4150

5187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.172

Hom.:

1755

Bravo

AF:

0.182

Asia WGS

AF:

0.420

AC:

1456

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

7.2

(source)

DANN

Benign

0.65

PhyloP100

4.2

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over