chr19-282766-T-C

Variant names:

• chr19-282766-T-C
• rs1600077293
• NM_003712.4:c.526A>G

Variant summary

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

The NM_003712.4(PLPP2):​c.526A>G​(p.Met176Val) 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLPP2 NM_003712.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.92

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.526A>G	p.Met176Val	missense_variant	Exon 4 of 6	ENST00000434325.7	NP_003703.1
PLPP2	NM_177543.3	c.589A>G	p.Met197Val	missense_variant	Exon 4 of 6		NP_808211.1
PLPP2	NM_177526.3	c.358A>G	p.Met120Val	missense_variant	Exon 4 of 6		NP_803545.1
PLPP2	XM_011528396.3	c.544A>G	p.Met182Val	missense_variant	Exon 4 of 6		XP_011526698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPP2	ENST00000434325.7	c.526A>G	p.Met176Val	missense_variant	Exon 4 of 6	1	NM_003712.4	ENSP00000388565.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461454 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727048

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 14, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.589A>G (p.M197V) alteration is located in exon 4 (coding exon 4) of the PLPP2 gene. This alteration results from a A to G substitution at nucleotide position 589, causing the methionine (M) at amino acid position 197 to be replaced by a valine (V). 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	Benign	0.26
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	20
DANN	Benign	0.74
DEOGEN2	Uncertain	0.63	.;D;.;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Benign	-0.66	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.9	D;.;.;.
REVEL	Uncertain	0.37
Sift	Uncertain	0.017	D;.;.;.
Sift4G	Benign	0.063	T;D;T;T
Polyphen		0.057	B;B;.;.
Vest4		0.68
MutPred		0.67		.;Gain of catalytic residue at M176 (P = 0.149);.;.;
MVP		0.73
MPC		0.41
ClinPred		0.77	D
GERP RS		3.1
Varity_R		0.57
gMVP		0.90

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: rs1600077293; hg19: chr19-282766;