Variant 19-19626578-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001395660.1(LPAR2):c.698C>T(p.Thr233Met) variant causes a missense change. The variant allele was found at a frequency of 0.00657 in 1,612,256 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0067 ( 52 hom. )

Consequence

LPAR2
NM_001395660.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.39

Variant links:

Genes affected

LPAR2 (HGNC:3168): (lysophosphatidic acid receptor 2) This gene encodes a member of family I of the G protein-coupled receptors, as well as the EDG family of proteins. This protein functions as a lysophosphatidic acid (LPA) receptor and contributes to Ca2+ mobilization, a critical cellular response to LPA in cells, through association with Gi and Gq proteins. An alternative splice variant has been described but its full length sequence has not been determined. [provided by RefSeq, Jul 2008]

LPAR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008259326).

BP6

Variant 19-19626578-G-A is Benign according to our data. Variant chr19-19626578-G-A is described in ClinVar as [Benign]. Clinvar id is 790435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 768 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPAR2	NM_001395660.1 linkuse as main transcript	c.698C>T	p.Thr233Met	missense_variant	2/3	ENST00000407877.8	NP_001382589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LPAR2	ENST00000407877.8 linkuse as main transcript	c.698C>T	p.Thr233Met	missense_variant	2/3	1	NM_001395660.1	ENSP00000384665	P1
LPAR2	ENST00000586703.1 linkuse as main transcript	c.698C>T	p.Thr233Met	missense_variant	2/3	1		ENSP00000465280	P1
LPAR2	ENST00000542587.5 linkuse as main transcript	c.698C>T	p.Thr233Met	missense_variant	5/6	2		ENSP00000443256	P1

Frequencies

GnomAD3 genomes

AF:

0.00505

AC:

769

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0186

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00700

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00529

AC:

1309

AN:

247610

Hom.:

AF XY:

0.00548

AC XY:

738

AN XY:

134560

show subpopulations

Gnomad AFR exome

AF:

0.000760

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00253

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.000558

Gnomad FIN exome

AF:

0.0194

Gnomad NFE exome

AF:

0.00683

Gnomad OTH exome

AF:

0.00626

GnomAD4 exome

AF:

0.00673

AC:

9829

AN:

1459932

Hom.:

Cov.:

AF XY:

0.00652

AC XY:

4738

AN XY:

726250

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00137

Gnomad4 ASJ exome

AF:

0.00242

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000604

Gnomad4 FIN exome

AF:

0.0190

Gnomad4 NFE exome

AF:

0.00747

Gnomad4 OTH exome

AF:

0.00515

GnomAD4 genome

AF:

0.00504

AC:

768

AN:

152324

Hom.:

Cov.:

AF XY:

0.00534

AC XY:

398

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00127

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0186

Gnomad4 NFE

AF:

0.00700

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00609

Hom.:

Bravo

AF:

0.00363

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00605

AC:

ExAC

AF:

0.00492

AC:

597

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.15

T;T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.83

.;.;T

MetaRNN

Benign

0.0083

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.59

N;N;N

MutationTaster

Benign

0.53

D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.83

.;N;N

REVEL

Benign

0.16

Sift

Benign

0.26

.;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.43

B;B;B

Vest4

0.11

MVP

0.79

MPC

0.51

ClinPred

0.018

GERP RS

3.1

Varity_R

0.052

gMVP

0.46

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

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