2-42763183-A-G

Position:

• chr2-42763183-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_148962.5(OXER1):​c.880T>C​(p.Cys294Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OXER1 NM_148962.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.253

Genes affected

OXER1 (HGNC:24884): (oxoeicosanoid receptor 1) Enables G protein-coupled receptor activity and icosanoid binding activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.947

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OXER1	NM_148962.5	c.880T>C	p.Cys294Arg	missense_variant	1/1	ENST00000378661.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OXER1	ENST00000378661.4	c.880T>C	p.Cys294Arg	missense_variant	1/1		NM_148962.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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 29, 2022

The c.997T>C (p.C333R) alteration is located in exon 1 (coding exon 1) of the OXER1 gene. This alteration results from a T to C substitution at nucleotide position 997, causing the cysteine (C) at amino acid position 333 to be replaced by an arginine (R). 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	0.79
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.86
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0051	T
MetaRNN	Pathogenic	0.95	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.17
Sift	Benign	0.039	D
Sift4G	Benign	0.098	T
Polyphen		0.97	D
Vest4		0.67
MutPred		0.79		Gain of solvent accessibility (P = 0.0584);
MVP		0.35
MPC		0.099
ClinPred		0.79	D
GERP RS		-2.9
Varity_R		0.42
gMVP		0.55

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: chr2-42990323;