NM_001395660.1:c.911G>A

Variant summary

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

The NM_001395660.1(LPAR2):​c.911G>A​(p.Arg304His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000558 in 1,614,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

LPAR2
NM_001395660.1 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04
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]

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=0.1446251).
BS2
High AC in GnomAd4 at 32 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LPAR2NM_001395660.1 linkc.911G>A p.Arg304His missense_variant Exon 3 of 3 ENST00000407877.8 NP_001382589.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LPAR2ENST00000407877.8 linkc.911G>A p.Arg304His missense_variant Exon 3 of 3 1 NM_001395660.1 ENSP00000384665.3 Q9HBW0
LPAR2ENST00000542587.5 linkc.911G>A p.Arg304His missense_variant Exon 6 of 6 2 ENSP00000443256.2 Q9HBW0
LPAR2ENST00000586703.1 linkc.911G>A p.Arg304His missense_variant Exon 3 of 3 1 ENSP00000465280.2 Q9HBW0

Frequencies

GnomAD3 genomes
AF:
0.000210
AC:
32
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000676
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251182
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135800
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
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:
0.0000397
AC:
58
AN:
1461824
Hom.:
0
Cov.:
29
AF XY:
0.0000440
AC XY:
32
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.000687
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000210
AC:
32
AN:
152316
Hom.:
0
Cov.:
32
AF XY:
0.000269
AC XY:
20
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.000674
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000228
Hom.:
0
Bravo
AF:
0.000185
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.920G>A (p.R307H) alteration is located in exon 3 (coding exon 2) of the LPAR2 gene. This alteration results from a G to A substitution at nucleotide position 920, causing the arginine (R) at amino acid position 307 to be replaced by a histidine (H). 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
0.15
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.50
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;T;T
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.82
.;.;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;M;M
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-1.3
.;N;N
REVEL
Benign
0.087
Sift
Benign
0.55
.;T;T
Sift4G
Benign
0.095
T;T;T
Polyphen
1.0
D;D;D
Vest4
0.34
MVP
0.56
MPC
1.4
ClinPred
0.14
T
GERP RS
4.6
Varity_R
0.11
gMVP
0.45

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.

Other links and lift over

dbSNP: rs145570005; hg19: chr19-19735201; API