6-27911875-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_033057.2(OR2B2):ā€‹c.445T>Cā€‹(p.Trp149Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000432 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00016 ( 0 hom., cov: 32)
Exomes š‘“: 0.00046 ( 0 hom. )

Consequence

OR2B2
NM_033057.2 missense

Scores

9
4
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.54
Variant links:
Genes affected
OR2B2 (HGNC:13966): (olfactory receptor family 2 subfamily B 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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.748

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR2B2NM_033057.2 linkc.445T>C p.Trp149Arg missense_variant 1/1 ENST00000303324.4 NP_149046.2 Q9GZK3A0A126GWD0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR2B2ENST00000303324.4 linkc.445T>C p.Trp149Arg missense_variant 1/16 NM_033057.2 ENSP00000304419.2 Q9GZK3

Frequencies

GnomAD3 genomes
AF:
0.000164
AC:
25
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000179
AC:
45
AN:
251290
Hom.:
0
AF XY:
0.000155
AC XY:
21
AN XY:
135794
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000378
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000460
AC:
672
AN:
1461838
Hom.:
0
Cov.:
33
AF XY:
0.000448
AC XY:
326
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000562
Gnomad4 OTH exome
AF:
0.000729
GnomAD4 genome
AF:
0.000164
AC:
25
AN:
152204
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.0000965
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000156
Hom.:
0
Bravo
AF:
0.000155
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000165
AC:
20
EpiCase
AF:
0.000491
EpiControl
AF:
0.000415

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 GeneticsApr 12, 2023The c.445T>C (p.W149R) alteration is located in exon 1 (coding exon 1) of the OR2B2 gene. This alteration results from a T to C substitution at nucleotide position 445, causing the tryptophan (W) at amino acid position 149 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
0.78
BayesDel_addAF
Uncertain
0.094
D
BayesDel_noAF
Pathogenic
0.21
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.068
T
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.014
T
MetaRNN
Pathogenic
0.75
D
MetaSVM
Benign
-0.42
T
MutationAssessor
Pathogenic
3.8
H
PrimateAI
Benign
0.34
T
PROVEAN
Pathogenic
-14
D
REVEL
Uncertain
0.39
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.56
MutPred
0.80
Gain of disorder (P = 0.0103);
MVP
0.81
MPC
0.86
ClinPred
0.99
D
GERP RS
4.4
Varity_R
0.95
gMVP
0.72

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

LitVar

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

Other links and lift over

dbSNP: rs200730241; hg19: chr6-27879653; API