19-282304-C-T

Variant names:

• chr19-282304-C-T
• rs1970191574
• NM_003712.4:c.547G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003712.4(PLPP2):​c.547G>A​(p.Val183Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: PLPP2 NM_003712.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPP2	NM_003712.4	c.547G>A	p.Val183Met	missense_variant	Exon 5 of 6	ENST00000434325.7	NP_003703.1
PLPP2	NM_177543.3	c.610G>A	p.Val204Met	missense_variant	Exon 5 of 6		NP_808211.1
PLPP2	NM_177526.3	c.379G>A	p.Val127Met	missense_variant	Exon 5 of 6		NP_803545.1
PLPP2	XM_011528396.3	c.565G>A	p.Val189Met	missense_variant	Exon 5 of 6		XP_011526698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPP2	ENST00000434325.7	c.547G>A	p.Val183Met	missense_variant	Exon 5 of 6	1	NM_003712.4	ENSP00000388565.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.610G>A (p.V204M) alteration is located in exon 5 (coding exon 5) of the PLPP2 gene. This alteration results from a G to A substitution at nucleotide position 610, causing the valine (V) at amino acid position 204 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	.;T;.;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.0042
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Uncertain	-0.25	T
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.87	N;.;.;.
REVEL	Uncertain	0.49
Sift	Uncertain	0.0030	D;.;.;.
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		0.99	D;P;.;.
Vest4		0.82
MutPred		0.66		.;Gain of MoRF binding (P = 0.1076);.;.;
MVP		0.86
MPC		1.0
ClinPred		0.83	D
GERP RS		2.4
Varity_R		0.32
gMVP		0.74

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: rs1970191574; hg19: chr19-282304;