NM_003712.4:c.410G>C

Variant names:

• chr19-287546-C-G
• NM_003712.4:c.410G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003712.4(PLPP2):​c.410G>C​(p.Arg137Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLPP2 NM_003712.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.327

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2064049).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPP2	NM_003712.4	c.410G>C	p.Arg137Pro	missense_variant	Exon 3 of 6	ENST00000434325.7	NP_003703.1
PLPP2	NM_177543.3	c.473G>C	p.Arg158Pro	missense_variant	Exon 3 of 6		NP_808211.1
PLPP2	NM_177526.3	c.242G>C	p.Arg81Pro	missense_variant	Exon 3 of 6		NP_803545.1
PLPP2	XM_011528396.3	c.428G>C	p.Arg143Pro	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.410G>C	p.Arg137Pro	missense_variant	Exon 3 of 6	1	NM_003712.4	ENSP00000388565.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.473G>C (p.R158P) alteration is located in exon 3 (coding exon 3) of the PLPP2 gene. This alteration results from a G to C substitution at nucleotide position 473, causing the arginine (R) at amino acid position 158 to be replaced by a proline (P). 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	Uncertain	0.43
BayesDel_addAF	Benign	-0.0040	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Uncertain	0.52	.;D;.;.;D
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.099	N
LIST_S2	Uncertain	0.86	D;D;D;D;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.21	T;T;T;T;T
MetaSVM	Benign	-0.88	T
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.6	D;D;D;.;.
REVEL	Benign	0.24
Sift	Benign	0.15	T;D;T;.;.
Sift4G	Benign	0.21	T;T;T;T;.
Polyphen		0.80	P;P;.;.;.
Vest4		0.53
MutPred		0.41		.;Gain of catalytic residue at C140 (P = 0.087);.;.;.;
MVP		0.63
MPC		1.1
ClinPred		0.50	T
GERP RS		-0.052
Varity_R		0.43
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-287546;