rs139689813
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_003712.4(PLPP2):āc.670G>Cā(p.Asp224His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 30)
Exomes š: 0.000012 ( 0 hom. )
Consequence
PLPP2
NM_003712.4 missense
NM_003712.4 missense
Scores
13
4
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.51
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
In a site Stabilizes the active site histidine for nucleophilic attack (size 0) in uniprot entity PLPP2_HUMAN
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.991
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PLPP2 | NM_003712.4 | c.670G>C | p.Asp224His | missense_variant | Exon 5 of 6 | ENST00000434325.7 | NP_003703.1 | |
| PLPP2 | NM_177543.3 | c.733G>C | p.Asp245His | missense_variant | Exon 5 of 6 | NP_808211.1 | ||
| PLPP2 | NM_177526.3 | c.502G>C | p.Asp168His | missense_variant | Exon 5 of 6 | NP_803545.1 | ||
| PLPP2 | XM_011528396.3 | c.688G>C | p.Asp230His | missense_variant | Exon 5 of 6 | XP_011526698.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461652Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 727162
GnomAD4 exome
AF:
AC:
17
AN:
1461652
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Cov.:
32
AF XY:
AC XY:
8
AN XY:
727162
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
30
Bravo
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
.;D;.;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;.;.
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;D;.;.
Vest4
MutPred
0.95
.;Gain of catalytic residue at L226 (P = 0.0544);.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at