rs1970305910

Variant names:

• chr19-288066-G-A
• rs1970305910
• NM_003712.4:c.158C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-288066-G-A
• chr19-288066-G-C

Variant summary

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

The NM_003712.4(PLPP2):​c.158C>T​(p.Thr53Ile) variant causes a missense change involving the alteration of a conserved nucleotide. 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)
• Consequence: PLPP2 NM_003712.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.26

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.158C>T	p.Thr53Ile	missense_variant	Exon 2 of 6	ENST00000434325.7	NP_003703.1
PLPP2	NM_177543.3	c.221C>T	p.Thr74Ile	missense_variant	Exon 2 of 6		NP_808211.1
PLPP2	XM_011528396.3	c.176C>T	p.Thr59Ile	missense_variant	Exon 2 of 6		XP_011526698.1
PLPP2	NM_177526.3	c.-11C>T		5_prime_UTR_variant	Exon 2 of 6		NP_803545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPP2	ENST00000434325.7	c.158C>T	p.Thr53Ile	missense_variant	Exon 2 of 6	1	NM_003712.4	ENSP00000388565.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.221C>T (p.T74I) alteration is located in exon 2 (coding exon 2) of the PLPP2 gene. This alteration results from a C to T substitution at nucleotide position 221, causing the threonine (T) at amino acid position 74 to be replaced by an isoleucine (I). 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	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	.;T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Uncertain	0.085	D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.9	D;.;.
REVEL	Uncertain	0.42
Sift	Uncertain	0.019	D;.;.
Sift4G	Uncertain	0.040	D;D;.
Polyphen		0.99	D;P;.
Vest4		0.81
MutPred		0.41		.;Loss of disorder (P = 0.0806);.;
MVP		0.90
MPC		1.0
ClinPred		0.99	D
GERP RS		2.3
Varity_R		0.18
gMVP		0.86

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: rs1970305910; hg19: chr19-288066;