dbSNP rs146880923: PLPPR2:p.Arg335His (chr19-11364351-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_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. 13/18 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

Publications

2 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

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 VariationId is 3421003.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022737.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLPPR2	NM_001393892.1	MANE Select	c.1020G>A	p.Ser340Ser	synonymous	Exon 10 of 10	NP_001380821.1	A0A8I5KWF3
PLPPR2	NM_001393894.1		c.1004G>A	p.Arg335His	missense	Exon 10 of 10	NP_001380823.1	Q96GM1-1
PLPPR2	NM_022737.3		c.1004G>A	p.Arg335His	missense	Exon 10 of 10	NP_073574.2	Q96GM1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLPPR2	ENST00000251473.9	TSL:1	c.1004G>A	p.Arg335His	missense	Exon 10 of 10	ENSP00000251473.4	Q96GM1-1
PLPPR2	ENST00000688289.1	MANE Select	c.1020G>A	p.Ser340Ser	synonymous	Exon 10 of 10	ENSP00000510269.1	A0A8I5KWF3
PLPPR2	ENST00000970838.1		c.1020G>A	p.Ser340Ser	synonymous	Exon 9 of 9	ENSP00000640897.1

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

GnomAD2 exomes

AF:

0.000236

AC:

AN:

169830

AF XY:

0.000244

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 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

African (AFR)

AF:

0.0000330

AC:

AN:

30260

American (AMR)

AF:

0.0000337

AC:

AN:

29712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19922

East Asian (EAS)

AF:

0.00

AC:

AN:

38588

South Asian (SAS)

AF:

0.0000142

AC:

AN:

70508

European-Finnish (FIN)

AF:

0.0000423

AC:

AN:

47334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5318

European-Non Finnish (NFE)

AF:

0.000264

AC:

281

AN:

1065734

Other (OTH)

AF:

0.0000890

AC:

AN:

56150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000171

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41562

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000324

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000271

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000241

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

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

PhyloP100

1.5

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

Mutation Taster

=98/2

polymorphism

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over