Genetic Variant PLPPR2:p.Arg371* (chr19-11364442-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001393892.1(PLPPR2):c.1111C>T(p.Arg371*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000132 in 1,519,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

PLPPR2
NM_001393892.1 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.44

Publications

0 publications found

Variant links:

Genes affected

PLPPR2 (HGNC:29566): (phospholipid phosphatase related 2) Predicted to enable lipid phosphatase activity and phosphatidate phosphatase activity. Predicted to be involved in phospholipid dephosphorylation; phospholipid metabolic process; and signal transduction. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLPPR2 links:

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ACMG classification

Classification was made for transcript

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_001393892.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLPPR2	NM_001393892.1	MANE Select	c.1111C>T	p.Arg371*	stop_gained	Exon 10 of 10	NP_001380821.1	A0A8I5KWF3
PLPPR2	NM_001393893.1		c.1111C>T	p.Arg371*	stop_gained	Exon 10 of 10	NP_001380822.1	A0A8I5KWF3
PLPPR2	NM_001170635.2		c.1036C>T	p.Arg346*	stop_gained	Exon 10 of 10	NP_001164106.1	Q96GM1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLPPR2	ENST00000688289.1	MANE Select	c.1111C>T	p.Arg371*	stop_gained	Exon 10 of 10	ENSP00000510269.1	A0A8I5KWF3
PLPPR2	ENST00000251473.9	TSL:1	c.*63C>T		3_prime_UTR	Exon 10 of 10	ENSP00000251473.4	Q96GM1-1
PLPPR2	ENST00000970838.1		c.1111C>T	p.Arg371*	stop_gained	Exon 9 of 9	ENSP00000640897.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000653

AC:

AN:

153230

AF XY:

0.0000122

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000135

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.32e-7

AC:

AN:

1366958

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

672002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30766

American (AMR)

AF:

0.00

AC:

AN:

31140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20496

East Asian (EAS)

AF:

0.00

AC:

AN:

38326

South Asian (SAS)

AF:

0.00

AC:

AN:

72516

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5394

European-Non Finnish (NFE)

AF:

9.33e-7

AC:

AN:

1071330

Other (OTH)

AF:

0.00

AC:

AN:

56614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.54

BayesDel_noAF

Pathogenic

0.54

CADD

Pathogenic

(source)

DANN

Benign

0.90

FATHMM_MKL

Benign

0.69

PhyloP100

2.4

Vest4

0.27

GERP RS

1.9

Mutation Taster

=42/158

disease causing

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over