dbSNP rs146880923: PLPPR2:p.Arg335His (chr19-11364351-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_022737.3(PLPPR2):c.1004G>A(p.Arg335His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,515,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

PLPPR2
NM_022737.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.53

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02708003).

BP6

Variant 19-11364351-G-A is Benign according to our data. Variant chr19-11364351-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3421003.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPPR2	NM_001393892.1 link	c.1020G>A	p.Ser340Ser	synonymous_variant	Exon 10 of 10	ENST00000688289.1	NP_001380821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLPPR2	ENST00000251473.9 link	c.1004G>A	p.Arg335His	missense_variant	Exon 10 of 10	1		ENSP00000251473.4	Q96GM1-1
PLPPR2	ENST00000688289.1 link	c.1020G>A	p.Ser340Ser	synonymous_variant	Exon 10 of 10		NM_001393892.1	ENSP00000510269.1	A0A8I5KWF3
PLPPR2	ENST00000591608.2 link	c.945G>A	p.Ser315Ser	synonymous_variant	Exon 10 of 10	2		ENSP00000466898.1	Q96GM1-2
PLPPR2	ENST00000588360.1 link	n.*136G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000324

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000236

AC:

AN:

169830

Hom.:

AF XY:

0.000244

AC XY:

AN XY:

90182

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000946

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000726

Gnomad NFE exome

AF:

0.000435

Gnomad OTH exome

AF:

0.000255

GnomAD4 exome

AF:

0.000213

AC:

291

AN:

1363526

Hom.:

Cov.:

AF XY:

0.000192

AC XY:

128

AN XY:

667928

show subpopulations

Gnomad4 AFR exome

AF:

0.0000330

Gnomad4 AMR exome

AF:

0.0000337

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000142

Gnomad4 FIN exome

AF:

0.0000423

Gnomad4 NFE exome

AF:

0.000264

Gnomad4 OTH exome

AF:

0.0000890

GnomAD4 genome

AF:

0.000171

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000241

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000241

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Sep 11, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0077

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.67

M_CAP

Benign

0.012

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.17

REVEL

Benign

0.051

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.013

Vest4

0.18

MVP

0.088

ClinPred

0.12

GERP RS

3.1

Varity_R

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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