16-55537579-A-G

Variant names:

• chr16-55537579-A-G
• NM_017839.5:c.799A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017839.5(LPCAT2):​c.799A>G​(p.Ile267Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 19/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LPCAT2 NM_017839.5 missense, splice_region
• Scores: Splicing: ADA: 0.0001092
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.684
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09529048).

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.799A>G	p.Ile267Val	missense splice_region	Exon 8 of 14	NP_060309.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPCAT2	ENST00000262134.10	TSL:1 MANE Select	c.799A>G	p.Ile267Val	missense splice_region	Exon 8 of 14	ENSP00000262134.5	Q7L5N7-1
	LPCAT2	ENST00000566915.5	TSL:1	n.881A>G		splice_region non_coding_transcript_exon	Exon 3 of 9
	LPCAT2	ENST00000947554.1		c.820A>G	p.Ile274Val	missense	Exon 8 of 14	ENSP00000617613.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	0.030
DANN	Benign	0.84
DEOGEN2	Benign	0.0089	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.68
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.21
Sift	Benign	0.087	T
Sift4G	Benign	0.12	T
Polyphen		0.0020	B
Vest4		0.18
MutPred		0.45		Gain of catalytic residue at I267 (P = 0.0238)
MVP		0.58
MPC		0.58
ClinPred		0.049	T
GERP RS		-7.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.017
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.078
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

Other links and lift over

hg19: chr16-55571491;