16-55529858-G-C

Variant names:

• chr16-55529858-G-C
• NM_017839.5:c.553G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92

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 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 rank	MANE	Protein	UniProt
LPCAT2	NM_017839.5	c.553G>C	p.Val185Leu	missense_variant	Exon 4 of 14	ENST00000262134.10	NP_060309.2
LPCAT2	XM_047434277.1	c.385G>C	p.Val129Leu	missense_variant	Exon 4 of 14		XP_047290233.1
LPCAT2	XM_005256006.4	c.553G>C	p.Val185Leu	missense_variant	Exon 4 of 9		XP_005256063.1
LPCAT2	XM_011523169.4	c.-240G>C		upstream_gene_variant			XP_011521471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPCAT2	ENST00000262134.10	c.553G>C	p.Val185Leu	missense_variant	Exon 4 of 14	1	NM_017839.5	ENSP00000262134.5
LPCAT2	ENST00000564084.1	c.124G>C	p.Val42Leu	missense_variant	Exon 2 of 7	3		ENSP00000457496.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459234 Hom.: 1 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725756

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 01, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Benign	0.91
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.098	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.57
Sift	Benign	0.040	D
Sift4G	Uncertain	0.058	T
Polyphen		0.73	P
Vest4		0.70
MutPred		0.61		Loss of MoRF binding (P = 0.1136);
MVP		0.75
MPC		0.82
ClinPred		0.74	D
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.

Other links and lift over

hg19: chr16-55563770;