chr19-11364430-G-A

Variant names:

• chr19-11364430-G-A
• rs1968137303
• NM_001393892.1:c.1099G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001393892.1(PLPPR2):​c.1099G>A​(p.Val367Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,368,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PLPPR2 NM_001393892.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2881378).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393892.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPPR2	NM_001393892.1	MANE Select	c.1099G>A	p.Val367Met	missense	Exon 10 of 10	NP_001380821.1	A0A8I5KWF3
	PLPPR2	NM_001393893.1		c.1099G>A	p.Val367Met	missense	Exon 10 of 10	NP_001380822.1	A0A8I5KWF3
	PLPPR2	NM_001170635.2		c.1024G>A	p.Val342Met	missense	Exon 10 of 10	NP_001164106.1	Q96GM1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPPR2	ENST00000688289.1	MANE Select	c.1099G>A	p.Val367Met	missense	Exon 10 of 10	ENSP00000510269.1	A0A8I5KWF3
	PLPPR2	ENST00000251473.9	TSL:1	c.*51G>A		3_prime_UTR	Exon 10 of 10	ENSP00000251473.4	Q96GM1-1
	PLPPR2	ENST00000970838.1		c.1099G>A	p.Val367Met	missense	Exon 9 of 9	ENSP00000640897.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1368558 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 672040

African (AFR) AF: 0.00 AC: 0 AN: 30718

American (AMR) AF: 0.00 AC: 0 AN: 31474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20332

East Asian (EAS) AF: 0.00 AC: 0 AN: 38674

South Asian (SAS) AF: 0.00 AC: 0 AN: 72212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5370

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1070200

Other (OTH) AF: 0.00 AC: 0 AN: 56616

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Benign	0.93
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.29	T
PhyloP100		2.4
PrimateAI	Pathogenic	0.84	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.31
MVP		0.41
MPC		0.89
GERP RS		4.2
gMVP		0.21
Mutation Taster		=93/7	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

Other links and lift over

dbSNP: rs1968137303; hg19: chr19-11475106;