6-29174486-C-T

Variant summary

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

The NM_030905.3(OR2J2):​c.851C>T​(p.Pro284Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,478 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

OR2J2
NM_030905.3 missense

Scores

2
5
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89
Variant links:
Genes affected
OR2J2 (HGNC:8260): (olfactory receptor family 2 subfamily J member 2) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
OR2J2NM_030905.3 linkuse as main transcriptc.851C>T p.Pro284Leu missense_variant 2/2 ENST00000641417.1 NP_112167.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR2J2ENST00000641417.1 linkuse as main transcriptc.851C>T p.Pro284Leu missense_variant 2/2 NM_030905.3 ENSP00000493401 P1
OR2J2ENST00000377167.3 linkuse as main transcriptc.851C>T p.Pro284Leu missense_variant 1/1 ENSP00000366372 P1

Frequencies

GnomAD3 genomes
AF:
0.0000330
AC:
5
AN:
151712
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000442
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000281
AC:
7
AN:
249314
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135252
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000167
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000315
AC:
46
AN:
1461766
Hom.:
0
Cov.:
34
AF XY:
0.0000385
AC XY:
28
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000333
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000330
AC:
5
AN:
151712
Hom.:
0
Cov.:
31
AF XY:
0.0000270
AC XY:
2
AN XY:
74072
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000657
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000442
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000340
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000248
AC:
3
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 26, 2023The c.851C>T (p.P284L) alteration is located in exon 1 (coding exon 1) of the OR2J2 gene. This alteration results from a C to T substitution at nucleotide position 851, causing the proline (P) at amino acid position 284 to be replaced by a leucine (L). 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
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
23
DANN
Uncertain
1.0
Eigen
Uncertain
0.21
Eigen_PC
Benign
-0.073
FATHMM_MKL
Benign
0.080
N
LIST_S2
Uncertain
0.92
.;D
M_CAP
Benign
0.00085
T
MetaRNN
Uncertain
0.48
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.21
T
PROVEAN
Pathogenic
-9.6
.;D
REVEL
Benign
0.088
Sift
Uncertain
0.0040
.;D
Sift4G
Pathogenic
0.0
.;D
Vest4
0.39
MutPred
0.60
Loss of glycosylation at P284 (P = 0.0909);Loss of glycosylation at P284 (P = 0.0909);
MVP
0.60
MPC
0.43
ClinPred
1.0
D
GERP RS
1.8
gMVP
0.42

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs368672235; hg19: chr6-29142263; COSMIC: COSV65847919; API