19-281424-G-C

Variant names:

• chr19-281424-G-C
• rs569329927
• NM_003712.4:c.831C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003712.4(PLPP2):​c.831C>G​(p.Asp277Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,358,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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: 30)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PLPP2 NM_003712.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064457595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPP2	NM_003712.4	c.831C>G	p.Asp277Glu	missense_variant	Exon 6 of 6	ENST00000434325.7	NP_003703.1
PLPP2	NM_177543.3	c.894C>G	p.Asp298Glu	missense_variant	Exon 6 of 6		NP_808211.1
PLPP2	NM_177526.3	c.663C>G	p.Asp221Glu	missense_variant	Exon 6 of 6		NP_803545.1
PLPP2	XM_011528396.3	c.849C>G	p.Asp283Glu	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.831C>G	p.Asp277Glu	missense_variant	Exon 6 of 6	1	NM_003712.4	ENSP00000388565.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1358364 Hom.: 0 Cov.: 32 AF XY: 0.00000149 AC XY: 1 AN XY: 670820

African (AFR) AF: 0.00 AC: 0 AN: 29530

American (AMR) AF: 0.00 AC: 0 AN: 33112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21240

East Asian (EAS) AF: 0.00 AC: 0 AN: 35008

South Asian (SAS) AF: 0.00 AC: 0 AN: 68962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5272

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1059814

Other (OTH) AF: 0.00 AC: 0 AN: 55234

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.7
DANN	Benign	0.87
DEOGEN2	Benign	0.033	.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.46	T;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.064	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.94	N;.;.
REVEL	Benign	0.0080
Sift	Benign	0.17	T;.;.
Sift4G	Benign	0.095	T;T;T
Polyphen		0.0060	B;B;.
Vest4		0.062
MutPred		0.18		.;Gain of disorder (P = 0.1468);.;
MVP		0.13
MPC		0.31
ClinPred		0.014	T
GERP RS		-1.9
Varity_R		0.040
gMVP		0.16
Mutation Taster		=97/3	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

Publications

LitVar

Other links and lift over

dbSNP: rs569329927; hg19: chr19-281424;