NM_003712.4:c.692A>T

Variant names:

• chr19-282159-T-A
• NM_003712.4:c.692A>T

Variant summary

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

The NM_003712.4(PLPP2):​c.692A>T​(p.Gln231Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: PLPP2 NM_003712.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.81

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPP2	NM_003712.4	c.692A>T	p.Gln231Leu	missense_variant	Exon 5 of 6	ENST00000434325.7	NP_003703.1
PLPP2	NM_177543.3	c.755A>T	p.Gln252Leu	missense_variant	Exon 5 of 6		NP_808211.1
PLPP2	NM_177526.3	c.524A>T	p.Gln175Leu	missense_variant	Exon 5 of 6		NP_803545.1
PLPP2	XM_011528396.3	c.710A>T	p.Gln237Leu	missense_variant	Exon 5 of 6		XP_011526698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPP2	ENST00000434325.7	c.692A>T	p.Gln231Leu	missense_variant	Exon 5 of 6	1	NM_003712.4	ENSP00000388565.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.755A>T (p.Q252L) alteration is located in exon 5 (coding exon 5) of the PLPP2 gene. This alteration results from a A to T substitution at nucleotide position 755, causing the glutamine (Q) at amino acid position 252 to be replaced by a leucine (L). 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	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	30
DANN	Benign	0.97
DEOGEN2	Uncertain	0.65	.;D;.;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Benign	-0.97	T
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.3	D;.;.;.
REVEL	Uncertain	0.48
Sift	Benign	1.0	T;.;.;.
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.056	B;B;.;.
Vest4		0.79
MutPred		0.56		.;Loss of catalytic residue at Q231 (P = 0.0071);.;.;
MVP		0.62
MPC		0.39
ClinPred		0.70	D
GERP RS		4.1
Varity_R		0.51
gMVP		0.63

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: chr19-282159;