19-43652319-CTT-GCG

Variant names:

• chr19-43652319-CTT-GCG
• NM_002659.4:c.658_660delAAGinsCGC
• PLAUR p.Lys220Arg

Variant summary

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

The NM_002659.4(PLAUR):​c.658_660delAAGinsCGC​(p.Lys220Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. K220Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLAUR NM_002659.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.53
• Publications: 0 publications found

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]

ENSG00000308028 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002659.4. 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
	PLAUR	NM_002659.4	MANE Select	c.658_660delAAGinsCGC	p.Lys220Arg	missense	N/A	NP_002650.1	Q03405-1
	PLAUR	NM_001005377.3		c.523_525delAAGinsCGC	p.Lys175Arg	missense	N/A	NP_001005377.1	Q03405-3
	PLAUR	NM_001005376.3		c.658_660delAAGinsCGC	p.Lys220Arg	missense	N/A	NP_001005376.1	Q03405-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAUR	ENST00000340093.8	TSL:1 MANE Select	c.658_660delAAGinsCGC	p.Lys220Arg	missense	N/A	ENSP00000339328.3	Q03405-1
	PLAUR	ENST00000221264.8	TSL:1	c.523_525delAAGinsCGC	p.Lys175Arg	missense	N/A	ENSP00000221264.3	Q03405-3
	PLAUR	ENST00000339082.7	TSL:1	c.658_660delAAGinsCGC	p.Lys220Arg	missense	N/A	ENSP00000342049.2	Q03405-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-44156471;