Genetic Variant PLPP2:p.Asp277Glu (chr19-281424-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003712.4(PLPP2):c.831C>G(p.Asp277Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,358,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

PLPP2
NM_003712.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.494

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.064457595).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003712.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLPP2	NM_003712.4	MANE Select	c.831C>G	p.Asp277Glu	missense	Exon 6 of 6	NP_003703.1	O43688-1
PLPP2	NM_177543.3		c.894C>G	p.Asp298Glu	missense	Exon 6 of 6	NP_808211.1	O43688-2
PLPP2	NM_177526.3		c.663C>G	p.Asp221Glu	missense	Exon 6 of 6	NP_803545.1	O43688-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLPP2	ENST00000434325.7	TSL:1 MANE Select	c.831C>G	p.Asp277Glu	missense	Exon 6 of 6	ENSP00000388565.2	O43688-1
PLPP2	ENST00000327790.7	TSL:5	c.894C>G	p.Asp298Glu	missense	Exon 6 of 6	ENSP00000329697.1	O43688-2
PLPP2	ENST00000951587.1		c.831C>G	p.Asp277Glu	missense	Exon 6 of 7	ENSP00000621646.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000147

AC:

AN:

1358364

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

670820

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29530

American (AMR)

AF:

0.00

AC:

AN:

33112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21240

East Asian (EAS)

AF:

0.00

AC:

AN:

35008

South Asian (SAS)

AF:

0.00

AC:

AN:

68962

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50192

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5272

European-Non Finnish (NFE)

AF:

0.00000189

AC:

AN:

1059814

Other (OTH)

AF:

0.00

AC:

AN:

55234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.7

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.033

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.46

M_CAP

Benign

0.0040

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

PhyloP100

-0.49

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.94

REVEL

Benign

0.0080

Sift

Benign

0.17

Sift4G

Benign

0.095

Polyphen

0.0060

Vest4

0.062

MutPred

0.18

Gain of disorder (P = 0.1468)

MVP

0.13

MPC

0.31

ClinPred

0.014

GERP RS

-1.9

Varity_R

0.040

gMVP

0.16

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over