19-11361269-G-T

Variant names:

• chr19-11361269-G-T
• NM_001393892.1:c.444G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001393892.1(PLPPR2):​c.444G>T​(p.Gln148His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLPPR2 NM_001393892.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

Genes affected

PLPPR2 (HGNC:29566): (phospholipid phosphatase related 2) Predicted to enable lipid phosphatase activity and phosphatidate phosphatase activity. Predicted to be involved in phospholipid dephosphorylation; phospholipid metabolic process; and signal transduction. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.951

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPPR2	NM_001393892.1	c.444G>T	p.Gln148His	missense_variant	Exon 6 of 10	ENST00000688289.1	NP_001380821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPPR2	ENST00000688289.1	c.444G>T	p.Gln148His	missense_variant	Exon 6 of 10		NM_001393892.1	ENSP00000510269.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.369G>T (p.Q123H) alteration is located in exon 6 (coding exon 4) of the PLPPR2 gene. This alteration results from a G to T substitution at nucleotide position 369, causing the glutamine (Q) at amino acid position 123 to be replaced by a histidine (H). 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	0.97
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D;.
Eigen	Benign	0.19
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Pathogenic	0.31	D
MetaRNN	Pathogenic	0.95	D;D
MetaSVM	Uncertain	-0.19	T
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-4.6	D;.
REVEL	Pathogenic	0.74
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.60	P;P
Vest4		0.95
MutPred		0.82		Gain of disorder (P = 0.2064);.;
MVP		0.35
MPC		1.7
ClinPred		1.0	D
GERP RS		0.66
Varity_R		0.85
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-11471945;