chr19-287742-C-A

Variant names:

• chr19-287742-C-A
• NM_003712.4:c.214G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003712.4(PLPP2):​c.214G>T​(p.Gly72Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLPP2 NM_003712.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.22

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.834

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPP2	NM_003712.4	c.214G>T	p.Gly72Trp	missense_variant	Exon 3 of 6	ENST00000434325.7	NP_003703.1
PLPP2	NM_177543.3	c.277G>T	p.Gly93Trp	missense_variant	Exon 3 of 6		NP_808211.1
PLPP2	NM_177526.3	c.46G>T	p.Gly16Trp	missense_variant	Exon 3 of 6		NP_803545.1
PLPP2	XM_011528396.3	c.232G>T	p.Gly78Trp	missense_variant	Exon 3 of 6		XP_011526698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPP2	ENST00000434325.7	c.214G>T	p.Gly72Trp	missense_variant	Exon 3 of 6	1	NM_003712.4	ENSP00000388565.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460910 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726656

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Uncertain	0.51	.;D;.;.;T
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;T;T;T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.83	D;D;D;D;D
MetaSVM	Uncertain	0.058	D
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-6.7	D;.;.;.;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.019	D;.;.;.;.
Sift4G	Uncertain	0.035	D;D;D;D;.
Polyphen		0.80	P;P;.;.;.
Vest4		0.91
MutPred		0.57		.;Loss of sheet (P = 0.0228);.;.;.;
MVP		0.77
MPC		0.94
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.84
gMVP		0.98

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-287742;