Genetic Variant LPCAT2:p.Val89Leu (chr16-55525601-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_017839.5(LPCAT2):c.265G>T(p.Val89Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,612,170 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. V89I) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0027 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 161 hom. )

Consequence

LPCAT2
NM_017839.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.07

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026696324).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00274 (416/152094) while in subpopulation SAS AF = 0.05 (241/4824). AF 95% confidence interval is 0.0448. There are 10 homozygotes in GnomAd4. There are 277 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPCAT2	NM_017839.5 link	c.265G>T	p.Val89Leu	missense_variant	Exon 2 of 14	ENST00000262134.10	NP_060309.2	Q7L5N7-1
LPCAT2	XM_047434277.1 link	c.97G>T	p.Val33Leu	missense_variant	Exon 2 of 14		XP_047290233.1
LPCAT2	XM_005256006.4 link	c.265G>T	p.Val89Leu	missense_variant	Exon 2 of 9		XP_005256063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPCAT2	ENST00000262134.10 link	c.265G>T	p.Val89Leu	missense_variant	Exon 2 of 14	1	NM_017839.5	ENSP00000262134.5		Q7L5N7-1
LPCAT2	ENST00000566911.1 link	n.375G>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

415

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.0237

Gnomad SAS

AF:

0.0499

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00384

GnomAD2 exomes

AF:

0.00794

AC:

1986

AN:

250032

AF XY:

0.0101

show subpopulations

Gnomad AFR exome

AF:

0.000310

Gnomad AMR exome

AF:

0.000176

Gnomad ASJ exome

AF:

0.00309

Gnomad EAS exome

AF:

0.0246

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.00477

GnomAD4 exome

AF:

0.00365

AC:

5322

AN:

1460076

Hom.:

161

Cov.:

AF XY:

0.00493

AC XY:

3579

AN XY:

726400

show subpopulations

African (AFR)

AF:

0.000330

AC:

AN:

33354

American (AMR)

AF:

0.0000674

AC:

AN:

44502

Ashkenazi Jewish (ASJ)

AF:

0.00257

AC:

AN:

26094

East Asian (EAS)

AF:

0.0241

AC:

955

AN:

39598

South Asian (SAS)

AF:

0.0447

AC:

3848

AN:

86012

European-Finnish (FIN)

AF:

0.000262

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000113

AC:

125

AN:

1111058

Other (OTH)

AF:

0.00478

AC:

288

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

223

446

670

893

1116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<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

AF:

0.00274

AC:

416

AN:

152094

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

277

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41502

American (AMR)

AF:

0.000262

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3466

East Asian (EAS)

AF:

0.0238

AC:

123

AN:

5178

South Asian (SAS)

AF:

0.0500

AC:

241

AN:

4824

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000177

AC:

AN:

67954

Other (OTH)

AF:

0.00427

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.0000563

Hom.:

Bravo

AF:

0.00125

ExAC

AF:

0.00839

AC:

1018

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.0018

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0027

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.020

PhyloP100

2.1

PrimateAI

Benign

0.29

PROVEAN

Benign

0.21

REVEL

Benign

0.069

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.10

MutPred

0.28

Gain of ubiquitination at K94 (P = 0.1679);

MVP

0.13

MPC

0.68

ClinPred

0.0026

GERP RS

3.2

Varity_R

0.055

gMVP

0.29

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over