19-19626638-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001395660.1(LPAR2):​c.638G>C​(p.Arg213Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 6.8e-7 (0 hom.)
• Consequence: LPAR2 NM_001395660.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62
• Publications: 0 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.897

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>C	p.Arg213Pro	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>C	p.Arg213Pro	missense	Exon 2 of 3	ENSP00000384665.3	Q9HBW0
	LPAR2	ENST00000542587.5	TSL:2	c.638G>C	p.Arg213Pro	missense	Exon 5 of 6	ENSP00000443256.2	Q9HBW0
	LPAR2	ENST00000586703.1	TSL:1	c.638G>C	p.Arg213Pro	missense	Exon 2 of 3	ENSP00000465280.2	Q9HBW0

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461062 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726834

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

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

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D
Eigen	Benign	0.14
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		2.6
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.79		Loss of MoRF binding (P = 0.0122)
MVP		0.45
MPC		1.6
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.88
gMVP		0.95
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;