15-64848614-A-C

Position:

• chr15-64848614-A-C

Variant summary

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

The NM_025201.5(PLEKHO2):​c.34A>C​(p.Lys12Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLEKHO2 NM_025201.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.44

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=0.15165505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHO2	NM_025201.5	c.34A>C	p.Lys12Gln	missense_variant	2/6	ENST00000323544.5	NP_079477.2
PLEKHO2	NM_001195059.2	c.13-6307A>C		intron_variant			NP_001181988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHO2	ENST00000323544.5	c.34A>C	p.Lys12Gln	missense_variant	2/6	1	NM_025201.5	ENSP00000326706.4
ENSG00000249240	ENST00000437723.1	c.34A>C	p.Lys12Gln	missense_variant	2/7	5		ENSP00000397942.1
PLEKHO2	ENST00000616065.4	c.13-6307A>C		intron_variant		1		ENSP00000483505.1
ENSG00000249240	ENST00000502574.1	n.168A>C		non_coding_transcript_exon_variant	2/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Feb 12, 2024

The c.34A>C (p.K12Q) alteration is located in exon 2 (coding exon 2) of the PLEKHO2 gene. This alteration results from a A to C substitution at nucleotide position 34, causing the lysine (K) at amino acid position 12 to be replaced by a glutamine (Q). 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	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0058	T;.
Eigen	Benign	0.012
Eigen_PC	Benign	0.092
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.59	N;N
REVEL	Benign	0.056
Sift	Uncertain	0.019	D;T
Sift4G	Benign	0.066	T;T
Polyphen		0.75	P;.
Vest4		0.38
MutPred		0.17		Loss of ubiquitination at K12 (P = 0.002);Loss of ubiquitination at K12 (P = 0.002);
MVP		0.27
MPC		0.34
ClinPred		0.56	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.16

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: chr15-65140813;