rs61738956

Variant names:

• chr19-281534-A-C
• NM_003712.4:c.721T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-281534-A-C
• chr19-281534-A-G

Variant summary

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

The NM_003712.4(PLPP2):​c.721T>G​(p.Cys241Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,340,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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: 30)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PLPP2 NM_003712.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

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=0.11517972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPP2	NM_003712.4	c.721T>G	p.Cys241Gly	missense_variant	Exon 6 of 6	ENST00000434325.7	NP_003703.1
PLPP2	NM_177543.3	c.784T>G	p.Cys262Gly	missense_variant	Exon 6 of 6		NP_808211.1
PLPP2	NM_177526.3	c.553T>G	p.Cys185Gly	missense_variant	Exon 6 of 6		NP_803545.1
PLPP2	XM_011528396.3	c.739T>G	p.Cys247Gly	missense_variant	Exon 6 of 6		XP_011526698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPP2	ENST00000434325.7	c.721T>G	p.Cys241Gly	missense_variant	Exon 6 of 6	1	NM_003712.4	ENSP00000388565.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1340362 Hom.: 0 Cov.: 32 AF XY: 0.00000152 AC XY: 1 AN XY: 658814

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000191

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.70
DEOGEN2	Uncertain	0.46	.;T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.050	T;T;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.90	T
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.79	N;.;.;.
REVEL	Benign	0.14
Sift	Benign	0.33	T;.;.;.
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.025	B;B;.;.
Vest4		0.14
MutPred		0.69		.;Gain of sheet (P = 0.0221);.;.;
MVP		0.22
MPC		0.47
ClinPred		0.078	T
GERP RS		0.22
Varity_R		0.085
gMVP		0.41

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: chr19-281534;