19-19626638-C-T

Variant names:

• chr19-19626638-C-T
• rs780463965
• NM_001395660.1:c.638G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001395660.1(LPAR2):​c.638G>A​(p.Arg213Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,461,062 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R213L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000015 (1 hom.)
• Consequence: LPAR2 NM_001395660.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.40982807).
• BS2: High AC in GnomAdExome4 at 22 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395660.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPAR2	NM_001395660.1	MANE Select	c.638G>A	p.Arg213Gln	missense	Exon 2 of 3	NP_001382589.1	Q9HBW0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPAR2	ENST00000407877.8	TSL:1 MANE Select	c.638G>A	p.Arg213Gln	missense	Exon 2 of 3	ENSP00000384665.3	Q9HBW0
	LPAR2	ENST00000542587.5	TSL:2	c.638G>A	p.Arg213Gln	missense	Exon 5 of 6	ENSP00000443256.2	Q9HBW0
	LPAR2	ENST00000586703.1	TSL:1	c.638G>A	p.Arg213Gln	missense	Exon 2 of 3	ENSP00000465280.2	Q9HBW0

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250156 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1461062 Hom.: 1 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 726834

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.22	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.26
Sift	Benign	0.055	T
Sift4G	Benign	0.18	T
Polyphen		0.95	P
Vest4		0.32
MutPred		0.80		Loss of MoRF binding (P = 0.0567)
MVP		0.54
MPC		0.78
ClinPred		0.62	D
GERP RS		4.1
Varity_R		0.21
gMVP		0.67
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs780463965; hg19: chr19-19737447; COSMIC: COSV52557688;