Genetic Variant LPCAT2:p.Glu168Asp (chr16-55528569-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_017839.5(LPCAT2):c.504G>C(p.Glu168Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

LPCAT2
NM_017839.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

Publications

0 publications found

Variant links:

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]

LPCAT2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.789

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017839.5. 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
	LPCAT2	NM_017839.5	MANE Select	c.504G>C	p.Glu168Asp	missense	Exon 3 of 14	NP_060309.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LPCAT2	ENST00000262134.10	TSL:1 MANE Select	c.504G>C	p.Glu168Asp	missense	Exon 3 of 14	ENSP00000262134.5	Q7L5N7-1
LPCAT2	ENST00000947554.1		c.504G>C	p.Glu168Asp	missense	Exon 3 of 14	ENSP00000617613.1
LPCAT2	ENST00000929287.1		c.504G>C	p.Glu168Asp	missense	Exon 3 of 13	ENSP00000599346.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461126

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726928

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111416

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.59

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.65

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.29

MetaRNN

Pathogenic

0.79

MetaSVM

Uncertain

0.13

MutationAssessor

Uncertain

2.9

PhyloP100

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.49

Sift

Uncertain

0.010

Sift4G

Uncertain

0.0090

Polyphen

0.28

Vest4

0.76

MutPred

0.64

Loss of disorder (P = 0.2032)

MVP

0.75

MPC

0.78

ClinPred

0.95

GERP RS

-0.84

PromoterAI

0.0074

Neutral

(source)

Varity_R

0.45

gMVP

0.76

Mutation Taster

=61/39

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over