chr19-282190-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003712.4(PLPP2):c.661C>T(p.His221Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
PLPP2
NM_003712.4 missense
NM_003712.4 missense
Scores
6
10
1
Clinical Significance
Conservation
PhyloP100: 7.55
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.921
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLPP2 | NM_003712.4 | c.661C>T | p.His221Tyr | missense_variant | 5/6 | ENST00000434325.7 | |
PLPP2 | NM_177543.3 | c.724C>T | p.His242Tyr | missense_variant | 5/6 | ||
PLPP2 | NM_177526.3 | c.493C>T | p.His165Tyr | missense_variant | 5/6 | ||
PLPP2 | XM_011528396.3 | c.679C>T | p.His227Tyr | missense_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLPP2 | ENST00000434325.7 | c.661C>T | p.His221Tyr | missense_variant | 5/6 | 1 | NM_003712.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 30
GnomAD3 genomes
Cov.:
30
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250974Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135756
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461674Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727158
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GnomAD4 genome Cov.: 30
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2022 | The c.724C>T (p.H242Y) alteration is located in exon 5 (coding exon 5) of the PLPP2 gene. This alteration results from a C to T substitution at nucleotide position 724, causing the histidine (H) at amino acid position 242 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;.;.
REVEL
Pathogenic
Sift
Uncertain
D;.;.;.
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;D;.;.
Vest4
MutPred
0.80
.;Loss of methylation at K219 (P = 0.0492);.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at