NM_014589.3:c.253C>A

Variant names:

• chr1-19922331-G-T
• rs760306746
• NM_014589.3:c.253C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014589.3(PLA2G2E):​c.253C>A​(p.Leu85Ile) 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 benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L85F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA2G2E NM_014589.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875
• Publications: 0 publications found

Genes affected

PLA2G2E (HGNC:13414): (phospholipase A2 group IIE) Enables calcium ion binding activity and calcium-dependent phospholipase A2 activity. Predicted to be involved in phospholipid metabolic process. Predicted to act upstream of or within low-density lipoprotein particle remodeling. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13867983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G2E	NM_014589.3	c.253C>A	p.Leu85Ile	missense_variant	Exon 3 of 4	ENST00000375116.3	NP_055404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G2E	ENST00000375116.3	c.253C>A	p.Leu85Ile	missense_variant	Exon 3 of 4	1	NM_014589.3	ENSP00000364257.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251308 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.6
DANN	Benign	0.93
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.88
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.029
Sift	Benign	0.093	T
Sift4G	Benign	0.20	T
Polyphen		0.0040	B
Vest4		0.37
MutPred		0.38		Gain of methylation at K80 (P = 0.0724);
MVP		0.17
MPC		0.25
ClinPred		0.073	T
GERP RS		-1.8
Varity_R		0.14
gMVP		0.20
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: rs760306746; hg19: chr1-20248824; COSMIC: COSV108219171;