19-43665356-CTC-TTT

Variant names:

• chr19-43665356-CTC-TTT
• NM_002659.4:c.268_270delGAGinsAAA
• PLAUR p.Glu90Lys

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_002659.4(PLAUR):c.268_270delGAGinsAAA (p.Glu90Lys) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.E90G: Uncertain_significance (ClinVar VariationId 2607848, 1 star); p.E90K: Uncertain_significance (ClinVar VariationId 2247581, 1 star)

• Frequency: Genomes: not found (cov: 30)
• Consequence: PLAUR NM_002659.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35
• 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:):

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_002659.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PLAUR NM_002659.4	MANE Select	c.268_270delGAGinsAAA p.Glu90Lys	missense	N/A	Prot: NP_002650.1 UniProt:
	PLAUR NM_001005377.3		c.268_270delGAGinsAAA p.Glu90Lys	missense	N/A	Prot: NP_001005377.1 UniProt:
	PLAUR NM_001301037.2		c.268_270delGAGinsAAA p.Glu90Lys	missense	N/A	Prot: NP_001287966.1 UniProt:

PLAUR NM_002659.4

MANE Select

HGVSc / HGVSpc.268_270delGAGinsAAAp.Glu90Lys

Exon rankN/A

missense

Prot: NP_002650.1UniProt: Q03405-1

PLAUR NM_001005377.3

HGVSc / HGVSpc.268_270delGAGinsAAAp.Glu90Lys

Exon rankN/A

missense

Prot: NP_001005377.1UniProt: Q03405-3

PLAUR NM_001301037.2

HGVSc / HGVSpc.268_270delGAGinsAAAp.Glu90Lys

Exon rankN/A

missense

Prot: NP_001287966.1UniProt: M0R1I2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PLAUR ENST00000340093.8	TSL:1MANE Select	c.268_270delGAGinsAAA p.Glu90Lys	missense	N/A	Prot: ENSP00000339328.3 UniProt:
	PLAUR ENST00000221264.8	TSL:1	c.268_270delGAGinsAAA p.Glu90Lys	missense	N/A	Prot: ENSP00000221264.3 UniProt:
	PLAUR ENST00000601723.5	TSL:1	c.268_270delGAGinsAAA p.Glu90Lys	missense	N/A	Prot: ENSP00000471881.1 UniProt:

PLAUR ENST00000340093.8

TSL:1MANE Select

HGVSc / HGVSpc.268_270delGAGinsAAAp.Glu90Lys

Exon rankN/A

missense

Prot: ENSP00000339328.3UniProt: Q03405-1

PLAUR ENST00000221264.8

TSL:1

HGVSc / HGVSpc.268_270delGAGinsAAAp.Glu90Lys

Exon rankN/A

missense

Prot: ENSP00000221264.3UniProt: Q03405-3

PLAUR ENST00000601723.5

TSL:1

HGVSc / HGVSpc.268_270delGAGinsAAAp.Glu90Lys

Exon rankN/A

missense

Prot: ENSP00000471881.1UniProt: M0R1I2

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:30
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:30

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Benign	3.4

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chr19-44169508;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar