Genetic Variant PLPP2:p.Cys241Gly (chr19-281534-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003712.4(PLPP2):c.721T>G(p.Cys241Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,340,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C241R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

PLPP2
NM_003712.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

Publications

0 publications found

Variant links:

Genes affected

PLPP2 (HGNC:9230): (phospholipid phosphatase 2) The protein encoded by this gene is a member of the phosphatidic acid phosphatase (PAP) family. PAPs convert phosphatidic acid to diacylglycerol, and function in de novo synthesis of glycerolipids as well as in receptor-activated signal transduction mediated by phospholipase D. This protein is similar to phosphatidic acid phosphatase type 2A (PPAP2A) and type 2B (PPAP2B). All three proteins contain 6 transmembrane regions, and a consensus N-glycosylation site. This protein has been shown to possess membrane associated PAP activity. Three alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

PLPP2 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11517972).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003712.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLPP2	NM_003712.4	MANE Select	c.721T>G	p.Cys241Gly	missense	Exon 6 of 6	NP_003703.1	O43688-1
PLPP2	NM_177543.3		c.784T>G	p.Cys262Gly	missense	Exon 6 of 6	NP_808211.1	O43688-2
PLPP2	NM_177526.3		c.553T>G	p.Cys185Gly	missense	Exon 6 of 6	NP_803545.1	O43688-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLPP2	ENST00000434325.7	TSL:1 MANE Select	c.721T>G	p.Cys241Gly	missense	Exon 6 of 6	ENSP00000388565.2	O43688-1
PLPP2	ENST00000327790.7	TSL:5	c.784T>G	p.Cys262Gly	missense	Exon 6 of 6	ENSP00000329697.1	O43688-2
PLPP2	ENST00000951587.1		c.721T>G	p.Cys241Gly	missense	Exon 6 of 7	ENSP00000621646.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000149

AC:

AN:

1340362

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

658814

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29596

American (AMR)

AF:

0.00

AC:

AN:

30638

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20336

East Asian (EAS)

AF:

0.00

AC:

AN:

35584

South Asian (SAS)

AF:

0.00

AC:

AN:

65434

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5224

European-Non Finnish (NFE)

AF:

0.00000191

AC:

AN:

1049546

Other (OTH)

AF:

0.00

AC:

AN:

54418

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Uncertain

0.46

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.050

M_CAP

Benign

0.040

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.90

PhyloP100

1.4

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.79

REVEL

Benign

0.14

Sift

Benign

0.33

Sift4G

Benign

0.33

Polyphen

0.025

Vest4

0.14

MutPred

0.69

Gain of sheet (P = 0.0221)

MVP

0.22

MPC

0.47

ClinPred

0.078

GERP RS

0.22

Varity_R

0.085

gMVP

0.41

Mutation Taster

=98/2

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over