Variant 1-23793194-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_007260.3(LYPLA2):c.154G>A(p.Val52Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

LYPLA2
NM_007260.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.65

Variant links:

Genes affected

LYPLA2 (HGNC:6738): (lysophospholipase 2) Lysophospholipases are enzymes that act on biological membranes to regulate the multifunctional lysophospholipids. There are alternatively spliced transcript variants described for this gene but the full length nature is not known yet. [provided by RefSeq, Jul 2008]

LYPLA2 links:

ENSG00000289835 (HGNC:):

ENSG00000289835 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22417027).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYPLA2	NM_007260.3 link	c.154G>A	p.Val52Ile	missense_variant	4/10	ENST00000374514.8	NP_009191.1	O95372A0A140VJC9
LYPLA2	XM_005245728.6 link	c.190G>A	p.Val64Ile	missense_variant	4/10		XP_005245785.1
LOC105376860	XR_947067.3 link	n.61+278C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYPLA2	ENST00000374514.8 link	c.154G>A	p.Val52Ile	missense_variant	4/10	1	NM_007260.3	ENSP00000363638.3		O95372

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251212

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135788

show subpopulations

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461688

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727160

show subpopulations

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.154G>A (p.V52I) alteration is located in exon 4 (coding exon 3) of the LYPLA2 gene. This alteration results from a G to A substitution at nucleotide position 154, causing the valine (V) at amino acid position 52 to be replaced by an isoleucine (I). 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

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.025

T;T;T;T;T;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.028

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.92

D;D;D;D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.22

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.44

N;.;.;.;.;.

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.17

N;N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.64

T;T;T;T;T;T

Sift4G

Benign

0.74

T;T;T;T;T;T

Polyphen

0.0060

B;.;P;B;.;.

Vest4

0.29

MutPred

0.59

Loss of methylation at K53 (P = 0.0577);.;Loss of methylation at K53 (P = 0.0577);Loss of methylation at K53 (P = 0.0577);Loss of methylation at K53 (P = 0.0577);Loss of methylation at K53 (P = 0.0577);

MVP

0.24

MPC

0.55

ClinPred

0.55

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over