Genetic Variant PLPP2:p.Arg85Cys (chr19-287703-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003712.4(PLPP2):c.253C>T(p.Arg85Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00707 in 1,613,922 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0073 ( 56 hom. )

Consequence

PLPP2
NM_003712.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.13

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009733021).

BP6

Variant 19-287703-G-A is Benign according to our data. Variant chr19-287703-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3024971.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPP2	NM_003712.4 link	c.253C>T	p.Arg85Cys	missense_variant	Exon 3 of 6	ENST00000434325.7	NP_003703.1	O43688-1
PLPP2	NM_177543.3 link	c.316C>T	p.Arg106Cys	missense_variant	Exon 3 of 6		NP_808211.1	O43688-2
PLPP2	NM_177526.3 link	c.85C>T	p.Arg29Cys	missense_variant	Exon 3 of 6		NP_803545.1	O43688-3
PLPP2	XM_011528396.3 link	c.271C>T	p.Arg91Cys	missense_variant	Exon 3 of 6		XP_011526698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPP2	ENST00000434325.7 link	c.253C>T	p.Arg85Cys	missense_variant	Exon 3 of 6	1	NM_003712.4	ENSP00000388565.2		O43688-1

Frequencies

GnomAD3 genomes

AF:

0.00460

AC:

700

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.00734

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00725

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00530

AC:

1331

AN:

251204

Hom.:

AF XY:

0.00551

AC XY:

748

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00447

Gnomad FIN exome

AF:

0.00836

Gnomad NFE exome

AF:

0.00712

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00733

AC:

10715

AN:

1461590

Hom.:

Cov.:

AF XY:

0.00720

AC XY:

5233

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.000984

Gnomad4 ASJ exome

AF:

0.0110

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00502

Gnomad4 FIN exome

AF:

0.00896

Gnomad4 NFE exome

AF:

0.00810

Gnomad4 OTH exome

AF:

0.00659

GnomAD4 genome

AF:

0.00458

AC:

698

AN:

152332

Hom.:

Cov.:

AF XY:

0.00435

AC XY:

324

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.00734

Gnomad4 NFE

AF:

0.00723

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00646

Hom.:

Bravo

AF:

0.00389

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00744

AC:

ExAC

AF:

0.00551

AC:

669

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00654

EpiControl

AF:

0.00693

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PLPP2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

.;T;.;.;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.76

T;T;T;T;T

MetaRNN

Benign

0.0097

T;T;T;T;T

MetaSVM

Uncertain

-0.033

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-4.3

D;.;.;.;.

REVEL

Benign

0.27

Sift

Uncertain

0.010

D;.;.;.;.

Sift4G

Uncertain

0.014

D;D;D;D;.

Polyphen

1.0

D;D;.;.;.

Vest4

0.47

MVP

0.88

MPC

1.1

ClinPred

0.028

GERP RS

5.0

Varity_R

0.26

gMVP

0.89

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over