Variant 16-55529858-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_017839.5(LPCAT2):c.553G>C(p.Val185Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,459,234 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 1 hom. )

Consequence

LPCAT2
NM_017839.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92

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 made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.807

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LPCAT2	NM_017839.5 linkuse as main transcript	c.553G>C	p.Val185Leu	missense_variant	4/14	ENST00000262134.10	NP_060309.2
LPCAT2	XM_047434277.1 linkuse as main transcript	c.385G>C	p.Val129Leu	missense_variant	4/14		XP_047290233.1
LPCAT2	XM_005256006.4 linkuse as main transcript	c.553G>C	p.Val185Leu	missense_variant	4/9		XP_005256063.1
LPCAT2	XM_011523169.4 linkuse as main transcript			upstream_gene_variant			XP_011521471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPCAT2	ENST00000262134.10 linkuse as main transcript	c.553G>C	p.Val185Leu	missense_variant	4/14	1	NM_017839.5	ENSP00000262134	P1	Q7L5N7-1
LPCAT2	ENST00000564084.1 linkuse as main transcript	c.127G>C	p.Val43Leu	missense_variant	2/7	3		ENSP00000457496

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1459234

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725756

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 01, 2023

The c.553G>C (p.V185L) alteration is located in exon 4 (coding exon 4) of the LPCAT2 gene. This alteration results from a G to C substitution at nucleotide position 553, causing the valine (V) at amino acid position 185 to be replaced by a leucine (L). 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

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Benign

0.91

DEOGEN2

Uncertain

0.53

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.098

MetaRNN

Pathogenic

0.81

MetaSVM

Uncertain

0.20

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.57

Sift

Benign

0.040

Sift4G

Uncertain

0.058

Polyphen

0.73

Vest4

0.70

MutPred

0.61

Loss of MoRF binding (P = 0.1136);

MVP

0.75

MPC

0.82

ClinPred

0.74

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.69

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over