Genetic Variant PLPP2:p.Ala180Gly (chr19-282753-G-C) – 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_003712.4(PLPP2):c.539C>G(p.Ala180Gly) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 30)

Failed GnomAD Quality Control

Consequence

PLPP2
NM_003712.4 missense, splice_region

Scores

Splicing: ADA: 0.001094

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.19

Publications

31 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:

Genome browser will be placed here

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;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PLPP2	NM_003712.4 link	c.539C>G	p.Ala180Gly	missense_variant, splice_region_variant	Exon 4 of 6	ENST00000434325.7	NP_003703.1
PLPP2	NM_177543.3 link	c.602C>G	p.Ala201Gly	missense_variant, splice_region_variant	Exon 4 of 6		NP_808211.1
PLPP2	NM_177526.3 link	c.371C>G	p.Ala124Gly	missense_variant, splice_region_variant	Exon 4 of 6		NP_803545.1
PLPP2	XM_011528396.3 link	c.557C>G	p.Ala186Gly	missense_variant, splice_region_variant	Exon 4 of 6		XP_011526698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPP2	ENST00000434325.7 link	c.539C>G	p.Ala180Gly	missense_variant, splice_region_variant	Exon 4 of 6	1	NM_003712.4	ENSP00000388565.2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151666

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151666

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74086

African (AFR)

AF:

0.00

AC:

AN:

41204

American (AMR)

AF:

0.00

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67934

Other (OTH)

AF:

0.00

AC:

AN:

2084

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.66

.;D;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.38

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.59

D;D;D;D

MetaSVM

Uncertain

-0.12

PhyloP100

6.2

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.5

D;D;.;.

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

D;D;.;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.89

P;P;.;.

Vest4

0.63

MutPred

0.51

.;Loss of stability (P = 0.0278);.;.;

MVP

0.81

MPC

0.73

ClinPred

0.99

GERP RS

-0.069

Varity_R

0.70

gMVP

0.77

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0011

dbscSNV1_RF

Benign

0.11

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over