rs2302524

Positions:

• chr19-43652320-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002659.4(PLAUR):​c.659A>G​(p.Lys220Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,613,684 control chromosomes in the GnomAD database, including 22,884 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (2334 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20550 hom.)
• Consequence: PLAUR NM_002659.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.53

Genes affected

PLAUR (HGNC:9053): (plasminogen activator, urokinase receptor) This gene encodes the receptor for urokinase plasminogen activator and, given its role in localizing and promoting plasmin formation, likely influences many normal and pathological processes related to cell-surface plasminogen activation and localized degradation of the extracellular matrix. It binds both the proprotein and mature forms of urokinase plasminogen activator and permits the activation of the receptor-bound pro-enzyme by plasmin. The protein lacks transmembrane or cytoplasmic domains and may be anchored to the plasma membrane by a glycosyl-phosphatidylinositol (GPI) moiety following cleavage of the nascent polypeptide near its carboxy-terminus. However, a soluble protein is also produced in some cell types. Alternative splicing results in multiple transcript variants encoding different isoforms. The proprotein experiences several post-translational cleavage reactions that have not yet been fully defined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002575338).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLAUR	NM_002659.4	c.659A>G	p.Lys220Arg	missense_variant	6/7	ENST00000340093.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAUR	ENST00000340093.8	c.659A>G	p.Lys220Arg	missense_variant	6/7	1	NM_002659.4	P1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25585 AN: 152024 Hom.: 2329 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0756

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.166

GnomAD3 exomes AF: 0.163 AC: 41001 AN: 251454 Hom.: 3719 AF XY: 0.159 AC XY: 21645 AN XY: 135894

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.257

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.0591

Gnomad SAS exome AF: 0.157

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.164 AC: 240282 AN: 1461542 Hom.: 20550 Cov.: 32 AF XY: 0.163 AC XY: 118859 AN XY: 727102

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.0872

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.168 AC: 25622 AN: 152142 Hom.: 2334 Cov.: 32 AF XY: 0.168 AC XY: 12504 AN XY: 74388

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.0754

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.164

Alfa AF: 0.164 Hom.: 5334

Bravo AF: 0.179

TwinsUK AF: 0.162 AC: 599

ALSPAC AF: 0.169 AC: 651

ESP6500AA AF: 0.197 AC: 870

ESP6500EA AF: 0.167 AC: 1432

ExAC AF: 0.163 AC: 19773

Asia WGS AF: 0.120 AC: 420 AN: 3478

EpiCase AF: 0.159

EpiControl AF: 0.161

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T;.;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.020
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.78	T;T;T;T
MetaRNN	Benign	0.0026	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N;.;.
MutationTaster	Benign	0.83	P;P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.79	N;N;N;.
REVEL	Benign	0.11
Sift	Benign	0.071	T;D;D;.
Sift4G	Uncertain	0.018	D;D;D;D
Polyphen		0.16	B;B;B;.
Vest4		0.13
MPC		0.12
ClinPred		0.017	T
GERP RS		4.5
Varity_R		0.35
gMVP		0.35

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: rs2302524; hg19: chr19-44156472; COSMIC: COSV55389007; COSMIC: COSV55389007;