19-19626659-G-T

Position:

• chr19-19626659-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000407877.8(LPAR2):​c.617C>A​(p.Thr206Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LPAR2 ENST00000407877.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPAR2	NM_001395660.1	c.617C>A	p.Thr206Asn	missense_variant	2/3	ENST00000407877.8	NP_001382589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPAR2	ENST00000407877.8	c.617C>A	p.Thr206Asn	missense_variant	2/3	1	NM_001395660.1	ENSP00000384665.3
LPAR2	ENST00000542587.5	c.617C>A	p.Thr206Asn	missense_variant	5/6	2		ENSP00000443256.2
LPAR2	ENST00000586703.1	c.617C>A	p.Thr206Asn	missense_variant	2/3	1		ENSP00000465280.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2023

The c.626C>A (p.T209N) alteration is located in exon 2 (coding exon 1) of the LPAR2 gene. This alteration results from a C to A substitution at nucleotide position 626, causing the threonine (T) at amino acid position 209 to be replaced by an asparagine (N). 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	Pathogenic	0.61
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Uncertain	0.42	T;T;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.95	.;.;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.4	M;M;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.8	.;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.011	.;D;D
Sift4G	Uncertain	0.028	D;D;D
Polyphen		0.84	P;P;P
Vest4		0.52
MutPred		0.63		Loss of phosphorylation at T209 (P = 0.0477);Loss of phosphorylation at T209 (P = 0.0477);Loss of phosphorylation at T209 (P = 0.0477);
MVP		0.91
MPC		1.0
ClinPred		0.66	D
GERP RS		0.67
Varity_R		0.22
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-19737468;