19-281424-G-A

Variant names:

• chr19-281424-G-A
• rs569329927
• NM_003712.4:c.831C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003712.4(PLPP2):​c.831C>T​(p.Asp277Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000736 in 1,358,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: PLPP2 NM_003712.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.494 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003712.4. 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
	PLPP2	NM_003712.4	MANE Select	c.831C>T	p.Asp277Asp	synonymous	Exon 6 of 6	NP_003703.1	O43688-1
	PLPP2	NM_177543.3		c.894C>T	p.Asp298Asp	synonymous	Exon 6 of 6	NP_808211.1	O43688-2
	PLPP2	NM_177526.3		c.663C>T	p.Asp221Asp	synonymous	Exon 6 of 6	NP_803545.1	O43688-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPP2	ENST00000434325.7	TSL:1 MANE Select	c.831C>T	p.Asp277Asp	synonymous	Exon 6 of 6	ENSP00000388565.2	O43688-1
	PLPP2	ENST00000327790.7	TSL:5	c.894C>T	p.Asp298Asp	synonymous	Exon 6 of 6	ENSP00000329697.1	O43688-2
	PLPP2	ENST00000951587.1		c.831C>T	p.Asp277Asp	synonymous	Exon 6 of 7	ENSP00000621646.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.36e-7 AC: 1 AN: 1358364 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 670820

African (AFR) AF: 0.00 AC: 0 AN: 29530

American (AMR) AF: 0.00 AC: 0 AN: 33112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21240

East Asian (EAS) AF: 0.00 AC: 0 AN: 35008

South Asian (SAS) AF: 0.00 AC: 0 AN: 68962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5272

European-Non Finnish (NFE) AF: 9.44e-7 AC: 1 AN: 1059814

Other (OTH) AF: 0.00 AC: 0 AN: 55234

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.68
PhyloP100		-0.49

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: rs569329927; hg19: chr19-281424;