16-55545745-T-C

Position:

• chr16-55545745-T-C

Variant summary

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

The NM_017839.5(LPCAT2):​c.863T>C​(p.Val288Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: LPCAT2 NM_017839.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71

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, 0.779

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPCAT2	NM_017839.5	c.863T>C	p.Val288Ala	missense_variant	9/14	ENST00000262134.10	NP_060309.2
LPCAT2	XM_047434277.1	c.695T>C	p.Val232Ala	missense_variant	9/14		XP_047290233.1
LPCAT2	XM_011523169.4	c.53T>C	p.Val18Ala	missense_variant	6/11		XP_011521471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPCAT2	ENST00000262134.10	c.863T>C	p.Val288Ala	missense_variant	9/14	1	NM_017839.5	ENSP00000262134	P1
LPCAT2	ENST00000566915.5	n.945T>C		non_coding_transcript_exon_variant	4/9	1
LPCAT2	ENST00000563095.5	n.261T>C		non_coding_transcript_exon_variant	1/4	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 2021

The c.863T>C (p.V288A) alteration is located in exon 9 (coding exon 9) of the LPCAT2 gene. This alteration results from a T to C substitution at nucleotide position 863, causing the valine (V) at amino acid position 288 to be replaced by an alanine (A). 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	0.32
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Pathogenic	3.3	M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.024	D
Polyphen		0.97	D
Vest4		0.64
MutPred		0.51		Gain of disorder (P = 0.0658);
MVP		0.88
MPC		1.1
ClinPred		0.93	D
GERP RS		6.0
Varity_R		0.18
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr16-55579657;