rs12595292

Positions:

• chr15-64861491-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000323544.5(PLEKHO2):​c.399G>A​(p.Lys133=) 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 ENST00000323544.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.16

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PLEKHO2	NM_025201.5	c.399G>A	p.Lys133=	synonymous_variant	5/6	ENST00000323544.5	NP_079477.2
PLEKHO2	NM_001195059.2	c.249G>A	p.Lys83=	synonymous_variant	4/5		NP_001181988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHO2	ENST00000323544.5	c.399G>A	p.Lys133=	synonymous_variant	5/6	1	NM_025201.5	ENSP00000326706	P1
PLEKHO2	ENST00000616065.4	c.249G>A	p.Lys83=	synonymous_variant	4/5	1		ENSP00000483505

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

GnomAD3 exomes AF: 0.223 AC: 50695 AN: 227122 Hom.: 8742 AF XY: 0.215 AC XY: 26433 AN XY: 123008

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 SAS exome AF: 0.166

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

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.321

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.790

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.190

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

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.195

Alfa AF: 0.154 Hom.: 792

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
DANN	Benign	0.65

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

Other links and lift over

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