chr15-64864929-C-T

Variant names:

• chr15-64864929-C-T
• rs753620849
• NM_025201.5:c.514C>T

Variant summary

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

The NM_025201.5(PLEKHO2):​c.514C>T​(p.Arg172Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,612,186 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: PLEKHO2 NM_025201.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.514C>T	p.Arg172Cys	missense	Exon 6 of 6	NP_079477.2
	PLEKHO2	NM_001195059.2		c.364C>T	p.Arg122Cys	missense	Exon 5 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.514C>T	p.Arg172Cys	missense	Exon 6 of 6	ENSP00000326706.4	Q8TD55-1
	PLEKHO2	ENST00000616065.4	TSL:1	c.364C>T	p.Arg122Cys	missense	Exon 5 of 5	ENSP00000483505.1	Q8TD55-2
	ENSG00000249240	ENST00000437723.1	TSL:5	c.483+3354C>T		intron	N/A	ENSP00000397942.1	C9J4A7

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152166 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000280 AC: 7 AN: 249772 AF XY: 0.0000445

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000356 AC: 52 AN: 1460020 Hom.: 0 Cov.: 33 AF XY: 0.0000262 AC XY: 19 AN XY: 726098

African (AFR) AF: 0.0000299 AC: 1 AN: 33444

American (AMR) AF: 0.0000224 AC: 1 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25984

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1110798

Other (OTH) AF: 0.00 AC: 0 AN: 60316

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152166 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000125 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.0064	T
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.34		Gain of catalytic residue at L173 (P = 0.0085)
MVP		0.51
MPC		0.58
ClinPred		0.78	D
GERP RS		4.7
Varity_R		0.30
gMVP		0.44
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs753620849; hg19: chr15-65157128; COSMIC: COSV60261920;