Genetic Variant LPAR2:p.Asn288Asn (chr19-19624439-A-G) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001395660.1(LPAR2):c.864T>C(p.Asn288Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00831 in 1,614,144 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0084 ( 73 hom. )

Consequence

LPAR2
NM_001395660.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.10

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 19-19624439-A-G is Benign according to our data. Variant chr19-19624439-A-G is described in ClinVar as [Benign]. Clinvar id is 788836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.1 with no splicing effect.

BS2

High AC in GnomAd4 at 1151 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPAR2	NM_001395660.1 link	c.864T>C	p.Asn288Asn	synonymous_variant	Exon 3 of 3	ENST00000407877.8	NP_001382589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LPAR2	ENST00000407877.8 link	c.864T>C	p.Asn288Asn	synonymous_variant	Exon 3 of 3	1	NM_001395660.1	ENSP00000384665.3	Q9HBW0
LPAR2	ENST00000542587.5 link	c.864T>C	p.Asn288Asn	synonymous_variant	Exon 6 of 6	2		ENSP00000443256.2	Q9HBW0
LPAR2	ENST00000586703.1 link	c.864T>C	p.Asn288Asn	synonymous_variant	Exon 3 of 3	1		ENSP00000465280.2	Q9HBW0

Frequencies

GnomAD3 genomes

AF:

0.00757

AC:

1152

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.00616

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0235

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00950

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00821

AC:

2063

AN:

251290

Hom.:

AF XY:

0.00818

AC XY:

1112

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00327

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00399

Gnomad FIN exome

AF:

0.0240

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.00839

AC:

12261

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00839

AC XY:

6102

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.00394

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00496

Gnomad4 FIN exome

AF:

0.0212

Gnomad4 NFE exome

AF:

0.00887

Gnomad4 OTH exome

AF:

0.00767

GnomAD4 genome

AF:

0.00756

AC:

1151

AN:

152300

Hom.:

Cov.:

AF XY:

0.00790

AC XY:

588

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00615

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0235

Gnomad4 NFE

AF:

0.00950

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00830

Hom.:

Bravo

AF:

0.00626

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00720

EpiControl

AF:

0.0103

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.29

DANN

Benign

0.61

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