15-64848608-G-T

Variant names:

• chr15-64848608-G-T
• rs150929841
• NM_025201.5:c.28G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025201.5(PLEKHO2):​c.28G>T​(p.Gly10Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G10S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PLEKHO2 NM_025201.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15145919).

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.28G>T	p.Gly10Cys	missense	Exon 2 of 6	NP_079477.2
	PLEKHO2	NM_001195059.2		c.13-6313G>T		intron	N/A	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.28G>T	p.Gly10Cys	missense	Exon 2 of 6	ENSP00000326706.4	Q8TD55-1
	ENSG00000249240	ENST00000437723.1	TSL:5	c.28G>T	p.Gly10Cys	missense	Exon 2 of 7	ENSP00000397942.1	C9J4A7
	PLEKHO2	ENST00000616065.4	TSL:1	c.13-6313G>T		intron	N/A	ENSP00000483505.1	Q8TD55-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.5
DANN	Benign	0.63
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.040
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.11
Sift	Benign	0.099	T
Sift4G	Uncertain	0.042	D
Polyphen		0.98	D
Vest4		0.24
MutPred		0.24		Loss of disorder (P = 0.0569)
MVP		0.48
MPC		0.11
ClinPred		0.46	T
GERP RS		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.18
gMVP		0.26
Mutation Taster		=100/0	polymorphism

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: rs150929841; hg19: chr15-65140807;