16-55545762-G-A

Variant names:

• chr16-55545762-G-A
• NM_017839.5:c.880G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017839.5(LPCAT2):​c.880G>A​(p.Glu294Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LPCAT2 NM_017839.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.80

Genes affected

LPCAT2 (HGNC:26032): (lysophosphatidylcholine acyltransferase 2) This gene encodes a member of the lysophospholipid acyltransferase family. The encoded enzyme may function in two ways: to catalyze the biosynthesis of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) from 1-O-alkyl-sn-glycero-3-phosphocholine, and to catalyze the synthesis of glycerophospholipid precursors from arachidonyl-CoA and lysophosphatidylcholine. The encoded protein may function in membrane biogenesis and production of platelet-activating factor in inflammatory cells. The enzyme may localize to the endoplasmic reticulum and the Golgi. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPCAT2	NM_017839.5	c.880G>A	p.Glu294Lys	missense_variant	Exon 9 of 14	ENST00000262134.10	NP_060309.2
LPCAT2	XM_047434277.1	c.712G>A	p.Glu238Lys	missense_variant	Exon 9 of 14		XP_047290233.1
LPCAT2	XM_011523169.4	c.70G>A	p.Glu24Lys	missense_variant	Exon 6 of 11		XP_011521471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPCAT2	ENST00000262134.10	c.880G>A	p.Glu294Lys	missense_variant	Exon 9 of 14	1	NM_017839.5	ENSP00000262134.5
LPCAT2	ENST00000566915.5	n.962G>A		non_coding_transcript_exon_variant	Exon 4 of 9	1
LPCAT2	ENST00000563095.5	n.278G>A		non_coding_transcript_exon_variant	Exon 1 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.880G>A (p.E294K) alteration is located in exon 9 (coding exon 9) of the LPCAT2 gene. This alteration results from a G to A substitution at nucleotide position 880, causing the glutamic acid (E) at amino acid position 294 to be replaced by a lysine (K). 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	Benign	0.070
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.10	T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Pathogenic	0.88	D
MutationAssessor	Pathogenic	3.4	M
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.45		Gain of ubiquitination at E294 (P = 0.0138);
MVP		0.89
MPC		0.88
ClinPred		0.93	D
GERP RS		6.0
Varity_R		0.36
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: chr16-55579674;