16-55537591-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_017839.5(LPCAT2):c.811A>G(p.Met271Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LPCAT2 NM_017839.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.972

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04152453).
• BP6: Variant 16-55537591-A-G is Benign according to our data. Variant chr16-55537591-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2525359.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPCAT2	NM_017839.5	c.811A>G	p.Met271Val	missense_variant	8/14	ENST00000262134.10
LPCAT2	XM_011523169.4	c.1A>G	p.Met1?	start_lost	5/11
LPCAT2	XM_047434277.1	c.643A>G	p.Met215Val	missense_variant	8/14
LPCAT2	XM_005256006.4	c.811A>G	p.Met271Val	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPCAT2	ENST00000262134.10	c.811A>G	p.Met271Val	missense_variant	8/14	1	NM_017839.5	P1
LPCAT2	ENST00000566915.5	n.893A>G		non_coding_transcript_exon_variant	3/9	1
LPCAT2	ENST00000564084.1	c.385A>G	p.Met129Val	missense_variant	6/7	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 250968 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135636

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461024 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726812

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	1.7
Dann	Benign	0.79
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.090	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.15
Sift	Benign	0.33	T
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.44		Gain of sheet (P = 0.0827);
MVP		0.25
MPC		0.71
ClinPred		0.030	T
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.048
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1450852439; hg19: chr16-55571503;