19-287600-A-T

Variant names:

• chr19-287600-A-T
• rs371103775
• NM_003712.4:c.356T>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003712.4(PLPP2):​c.356T>A​(p.Met119Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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: 0.0000014 (0 hom.)
• Consequence: PLPP2 NM_003712.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.94

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38107386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPP2	NM_003712.4	c.356T>A	p.Met119Lys	missense_variant	Exon 3 of 6	ENST00000434325.7	NP_003703.1
PLPP2	NM_177543.3	c.419T>A	p.Met140Lys	missense_variant	Exon 3 of 6		NP_808211.1
PLPP2	NM_177526.3	c.188T>A	p.Met63Lys	missense_variant	Exon 3 of 6		NP_803545.1
PLPP2	XM_011528396.3	c.374T>A	p.Met125Lys	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.356T>A	p.Met119Lys	missense_variant	Exon 3 of 6	1	NM_003712.4	ENSP00000388565.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251390 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135888

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461564 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727068

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	19
DANN	Benign	0.83
DEOGEN2	Uncertain	0.50	.;D;.;.;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.54
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.38	T;T;T;T;T
MetaSVM	Benign	-0.67	T
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	N;.;.;.;.
REVEL	Uncertain	0.45
Sift	Benign	0.030	D;.;.;.;.
Sift4G	Uncertain	0.055	T;D;D;D;.
Polyphen		0.73	P;B;.;.;.
Vest4		0.85
MutPred		0.69		.;Gain of ubiquitination at M119 (P = 0.0797);.;.;.;
MVP		0.52
MPC		0.71
ClinPred		0.16	T
GERP RS		0.46
Varity_R		0.74
gMVP		0.94

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

LitVar

Other links and lift over

dbSNP: rs371103775; hg19: chr19-287600;