rs11540666

chr19-11362682-C-Gchr19-11362682-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 11/17 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.760

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]

ACMG classification

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/exons	MANE	UniProt
PLPPR2	NM_001393892.1	c.833C>G	p.Thr278Ser	missense_variant	7/10	ENST00000688289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLPPR2	ENST00000688289.1	c.833C>G	p.Thr278Ser	missense_variant	7/10		NM_001393892.1	P3

Frequencies

GnomAD3 genomes AF: 0.0572 AC: 8706 AN: 152204 Hom.: 372 Cov.: 32

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

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.: 32 AF XY: 0.0768 AC XY: 55713 AN XY: 725760

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.: 32 AF XY: 0.0585 AC XY: 4356 AN XY: 74494

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.: 92

Bravo AF: 0.0479

TwinsUK AF: 0.0742 AC: 275

ALSPAC AF: 0.0711 AC: 274

ESP6500AA AF: 0.0150 AC: 66

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	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.37	T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.042
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.79	T;T
MetaRNN	Benign	0.0022	T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	0.64	N;N
PrimateAI	Uncertain	0.58	T
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	T
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

Other links and lift over

dbSNP: rs11540666; hg19: chr19-11473358; COSMIC: COSV52259405; COSMIC: COSV52259405;