19-11364442-C-A

Variant names:

• chr19-11364442-C-A
• rs1489854169
• NM_001393892.1:c.1111C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001393892.1(PLPPR2):​c.1111C>A​(p.Arg371Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000732 in 1,366,958 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: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: PLPPR2 NM_001393892.1 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP7: Synonymous conserved (PhyloP=2.44 with no splicing effect.

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.1111C>A	p.Arg371Arg	synonymous	Exon 10 of 10	NP_001380821.1	A0A8I5KWF3
	PLPPR2	NM_001393893.1		c.1111C>A	p.Arg371Arg	synonymous	Exon 10 of 10	NP_001380822.1	A0A8I5KWF3
	PLPPR2	NM_001170635.2		c.1036C>A	p.Arg346Arg	synonymous	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.1111C>A	p.Arg371Arg	synonymous	Exon 10 of 10	ENSP00000510269.1	A0A8I5KWF3
	PLPPR2	ENST00000251473.9	TSL:1	c.*63C>A		3_prime_UTR	Exon 10 of 10	ENSP00000251473.4	Q96GM1-1
	PLPPR2	ENST00000970838.1		c.1111C>A	p.Arg371Arg	synonymous	Exon 9 of 9	ENSP00000640897.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.32e-7 AC: 1 AN: 1366958 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 672002

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30766

American (AMR) AF: 0.00 AC: 0 AN: 31140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20496

East Asian (EAS) AF: 0.00 AC: 0 AN: 38326

South Asian (SAS) AF: 0.00 AC: 0 AN: 72516

European-Finnish (FIN) AF: 0.0000248 AC: 1 AN: 40376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5394

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071330

Other (OTH) AF: 0.00 AC: 0 AN: 56614

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.8
DANN	Benign	0.88
PhyloP100		2.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1489854169; hg19: chr19-11475118;