chr19-282753-G-C

Variant names:

• chr19-282753-G-C
• rs1138439
• NM_003712.4:c.539C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003712.4(PLPP2):​c.539C>G​(p.Ala180Gly) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: PLPP2 NM_003712.4 missense, splice_region
• Scores: Splicing: ADA: 0.001094
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.19
• Publications: 31 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 2 ACMG points.

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

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPP2	NM_003712.4	MANE Select	c.539C>G	p.Ala180Gly	missense splice_region	Exon 4 of 6	NP_003703.1
	PLPP2	NM_177543.3		c.602C>G	p.Ala201Gly	missense splice_region	Exon 4 of 6	NP_808211.1
	PLPP2	NM_177526.3		c.371C>G	p.Ala124Gly	missense splice_region	Exon 4 of 6	NP_803545.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPP2	ENST00000434325.7	TSL:1 MANE Select	c.539C>G	p.Ala180Gly	missense splice_region	Exon 4 of 6	ENSP00000388565.2
	PLPP2	ENST00000327790.7	TSL:5	c.602C>G	p.Ala201Gly	missense splice_region	Exon 4 of 6	ENSP00000329697.1
	PLPP2	ENST00000269812.7	TSL:3	c.371C>G	p.Ala124Gly	missense splice_region	Exon 4 of 6	ENSP00000269812.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151666 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 39

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151666 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74086

African (AFR) AF: 0.00 AC: 0 AN: 41204

American (AMR) AF: 0.00 AC: 0 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67934

Other (OTH) AF: 0.00 AC: 0 AN: 2084

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Uncertain	0.66	D
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.38
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	-0.12	T
PhyloP100		6.2
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.89	P
Vest4		0.63
MutPred		0.51		Loss of stability (P = 0.0278)
MVP		0.81
MPC		0.73
ClinPred		0.99	D
GERP RS		-0.069
Varity_R		0.70
gMVP		0.77
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0011
dbscSNV1_RF	Benign	0.11
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

Other links and lift over

dbSNP: rs1138439; hg19: chr19-282753;