16-55525601-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017839.5(LPCAT2):c.265G>A(p.Val89Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00348 in 1,612,162 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (49 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (49 hom.)
• Consequence: LPCAT2 NM_017839.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.07

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002805978).
• BP6: Variant 16-55525601-G-A is Benign according to our data. Variant chr16-55525601-G-A is described in ClinVar as [Benign]. Clinvar id is 768779.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0145 (2207/152088) while in subpopulation AFR AF= 0.0467 (1936/41496). AF 95% confidence interval is 0.0449. There are 49 homozygotes in gnomad4. There are 1054 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPCAT2	NM_017839.5	c.265G>A	p.Val89Ile	missense_variant	2/14	ENST00000262134.10
LPCAT2	XM_047434277.1	c.97G>A	p.Val33Ile	missense_variant	2/14
LPCAT2	XM_005256006.4	c.265G>A	p.Val89Ile	missense_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPCAT2	ENST00000262134.10	c.265G>A	p.Val89Ile	missense_variant	2/14	1	NM_017839.5	P1
LPCAT2	ENST00000566911.1	n.375G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2206 AN: 151970 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00683

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000383

Gnomad OTH AF: 0.00815

GnomAD3 exomes AF: 0.00521 AC: 1303 AN: 250032 Hom.: 18 AF XY: 0.00422 AC XY: 570 AN XY: 135190

Gnomad AFR exome AF: 0.0452

Gnomad AMR exome AF: 0.00270

Gnomad ASJ exome AF: 0.0384

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000539

Gnomad OTH exome AF: 0.00509

GnomAD4 exome AF: 0.00233 AC: 3408 AN: 1460074 Hom.: 49 Cov.: 30 AF XY: 0.00211 AC XY: 1535 AN XY: 726406

Gnomad4 AFR exome AF: 0.0458

Gnomad4 AMR exome AF: 0.00321

Gnomad4 ASJ exome AF: 0.0381

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.000281

Gnomad4 NFE exome AF: 0.000261

Gnomad4 OTH exome AF: 0.00678

GnomAD4 genome AF: 0.0145 AC: 2207 AN: 152088 Hom.: 49 Cov.: 32 AF XY: 0.0142 AC XY: 1054 AN XY: 74368

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.00675

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000383

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00537 Hom.: 30

Bravo AF: 0.0166

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0428 AC: 188

ESP6500EA AF: 0.00163 AC: 14

ExAC AF: 0.00569 AC: 691

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	15
Dann	Benign	0.95
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.52	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.071
Sift	Benign	0.33	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.093
MVP		0.24
MPC		0.57
ClinPred		0.0039	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.042
gMVP		0.17

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

LitVar

Other links and lift over

dbSNP: rs61744474; hg19: chr16-55559513;