PLPP2 p.Gly72Arg

Variant names:

• chr19-287742-C-G
• NM_003712.4:c.214G>C
• PLPP2 p.Gly72Arg

Your query was ambiguous. Multiple possible variants found:

• chr19-287742-C-G
• chr19-287742-C-T
• chr19-287740-CCC-ACG
• chr19-287740-CCC-GCG
• chr19-287740-CCC-TCG
• chr19-287740-CCC-TCT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003712.4(PLPP2):​c.214G>C​(p.Gly72Arg) 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLPP2 NM_003712.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.22
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003712.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPP2	NM_003712.4	MANE Select	c.214G>C	p.Gly72Arg	missense	Exon 3 of 6	NP_003703.1	O43688-1
	PLPP2	NM_177543.3		c.277G>C	p.Gly93Arg	missense	Exon 3 of 6	NP_808211.1	O43688-2
	PLPP2	NM_177526.3		c.46G>C	p.Gly16Arg	missense	Exon 3 of 6	NP_803545.1	O43688-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPP2	ENST00000434325.7	TSL:1 MANE Select	c.214G>C	p.Gly72Arg	missense	Exon 3 of 6	ENSP00000388565.2	O43688-1
	PLPP2	ENST00000327790.7	TSL:5	c.277G>C	p.Gly93Arg	missense	Exon 3 of 6	ENSP00000329697.1	O43688-2
	PLPP2	ENST00000951587.1		c.214G>C	p.Gly72Arg	missense	Exon 3 of 7	ENSP00000621646.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.25	D
PhyloP100		7.2
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.037	D
PromoterAI		-0.0074	Neutral
Varity_R		0.82
gMVP		0.99
Mutation Taster		=59/41	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-287742;