15-64865208-G-T

Position:

• chr15-64865208-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025201.5(PLEKHO2):​c.793G>T​(p.Val265Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: PLEKHO2 NM_025201.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.392

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10739803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHO2	NM_025201.5	c.793G>T	p.Val265Phe	missense_variant	6/6	ENST00000323544.5	NP_079477.2
PLEKHO2	NM_001195059.2	c.643G>T	p.Val215Phe	missense_variant	5/5		NP_001181988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHO2	ENST00000323544.5	c.793G>T	p.Val265Phe	missense_variant	6/6	1	NM_025201.5	ENSP00000326706.4
PLEKHO2	ENST00000616065.4	c.643G>T	p.Val215Phe	missense_variant	5/5	1		ENSP00000483505.1
ENSG00000249240	ENST00000437723.1	c.483+3633G>T		intron_variant		5		ENSP00000397942.1
ENSG00000249240	ENST00000502574.1	n.617+3633G>T		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.793G>T (p.V265F) alteration is located in exon 6 (coding exon 6) of the PLEKHO2 gene. This alteration results from a G to T substitution at nucleotide position 793, causing the valine (V) at amino acid position 265 to be replaced by a phenylalanine (F). 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	0.073
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.68
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0074	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.6	.;N
REVEL	Benign	0.083
Sift	Uncertain	0.0070	.;D
Sift4G	Benign	0.52	T;T
Polyphen		0.77	P;P
Vest4		0.18
MutPred		0.26		.;Gain of glycosylation at P262 (P = 0.0983);
MVP		0.14
MPC		0.24
ClinPred		0.83	D
GERP RS		-5.5
Varity_R		0.18
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-65157407;