rs12595292

Variant names:

• chr15-64861491-G-A
• rs12595292
• NM_025201.5:c.399G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.16
• Publications: 27 publications found

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]

ENSG00000249240 (HGNC:):

ACMG classification

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.

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.399G>A	p.Lys133Lys	synonymous	Exon 5 of 6	NP_079477.2
	PLEKHO2	NM_001195059.2		c.249G>A	p.Lys83Lys	synonymous	Exon 4 of 5	NP_001181988.1	Q8TD55-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHO2	ENST00000323544.5	TSL:1 MANE Select	c.399G>A	p.Lys133Lys	synonymous	Exon 5 of 6	ENSP00000326706.4	Q8TD55-1
	PLEKHO2	ENST00000616065.4	TSL:1	c.249G>A	p.Lys83Lys	synonymous	Exon 4 of 5	ENSP00000483505.1	Q8TD55-2
	ENSG00000249240	ENST00000437723.1	TSL:5	c.399G>A	p.Lys133Lys	synonymous	Exon 5 of 7	ENSP00000397942.1	C9J4A7

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26794 AN: 152122 Hom.: 3404 Cov.: 32

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

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.: 31 AF XY: 0.171 AC XY: 122910 AN XY: 719628

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

GnomAD4 genome AF: 0.176 AC: 26816 AN: 152240 Hom.: 3410 Cov.: 32 AF XY: 0.182 AC XY: 13532 AN XY: 74426

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: 58 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10147 AN: 68014

Other (OTH) AF: 0.195 AC: 411 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	7.2
DANN	Benign	0.65
PhyloP100		4.2
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12595292; hg19: chr15-65153690; COSMIC: COSV60261865;