dbSNP rs11540666: PLPPR2:p.Thr278Ser (chr19-11362682-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001393892.1(PLPPR2):c.833C>G(p.Thr278Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 1,611,896 control chromosomes in the GnomAD database, including 4,839 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.057 ( 372 hom., cov: 32)

Exomes 𝑓: 0.075 ( 4467 hom. )

Consequence

PLPPR2
NM_001393892.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.760

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022139847).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPPR2	NM_001393892.1 link	c.833C>G	p.Thr278Ser	missense_variant	Exon 7 of 10	ENST00000688289.1	NP_001380821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPPR2	ENST00000688289.1 link	c.833C>G	p.Thr278Ser	missense_variant	Exon 7 of 10		NM_001393892.1	ENSP00000510269.1		A0A8I5KWF3

Frequencies

GnomAD3 genomes

AF:

0.0572

AC:

8706

AN:

152204

Hom.:

372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0132

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.0355

Gnomad ASJ

AF:

0.0573

Gnomad EAS

AF:

0.0416

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.0938

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0781

Gnomad OTH

AF:

0.0501

GnomAD3 exomes

AF:

0.0685

AC:

17072

AN:

249252

Hom.:

755

AF XY:

0.0747

AC XY:

10077

AN XY:

134852

show subpopulations

Gnomad AFR exome

AF:

0.0123

Gnomad AMR exome

AF:

0.0269

Gnomad ASJ exome

AF:

0.0542

Gnomad EAS exome

AF:

0.0377

Gnomad SAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.0920

Gnomad NFE exome

AF:

0.0734

Gnomad OTH exome

AF:

0.0669

GnomAD4 exome

AF:

0.0746

AC:

108957

AN:

1459574

Hom.:

4467

Cov.:

AF XY:

0.0768

AC XY:

55713

AN XY:

725760

show subpopulations

Gnomad4 AFR exome

AF:

0.0112

Gnomad4 AMR exome

AF:

0.0274

Gnomad4 ASJ exome

AF:

0.0512

Gnomad4 EAS exome

AF:

0.0317

Gnomad4 SAS exome

AF:

0.134

Gnomad4 FIN exome

AF:

0.0952

Gnomad4 NFE exome

AF:

0.0754

Gnomad4 OTH exome

AF:

0.0698

GnomAD4 genome

AF:

0.0572

AC:

8706

AN:

152322

Hom.:

372

Cov.:

AF XY:

0.0585

AC XY:

4356

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0132

Gnomad4 AMR

AF:

0.0354

Gnomad4 ASJ

AF:

0.0573

Gnomad4 EAS

AF:

0.0413

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.0938

Gnomad4 NFE

AF:

0.0781

Gnomad4 OTH

AF:

0.0501

Alfa

AF:

0.0525

Hom.:

Bravo

AF:

0.0479

TwinsUK

AF:

0.0742

AC:

275

ALSPAC

AF:

0.0711

AC:

274

ESP6500AA

AF:

0.0150

AC:

ESP6500EA

AF:

0.0750

AC:

645

ExAC

AF:

0.0688

AC:

8355

Asia WGS

AF:

0.0870

AC:

305

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.042

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.79

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-0.93

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.15

Sift

Benign

0.055

T;.

Sift4G

Uncertain

0.015

D;D

Polyphen

0.69

P;P

Vest4

0.19

MutPred

0.36

Loss of sheet (P = 0.1158);.;

MPC

1.2

ClinPred

0.020

GERP RS

4.4

Varity_R

0.20

gMVP

0.34

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over