2-240029732-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001005853.1(OR6B2):ā€‹c.698G>Cā€‹(p.Gly233Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

OR6B2
NM_001005853.1 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.07
Variant links:
Genes affected
OR6B2 (HGNC:15041): (olfactory receptor family 6 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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2914363).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR6B2NM_001005853.1 linkuse as main transcriptc.698G>C p.Gly233Ala missense_variant 1/1 ENST00000319423.5 NP_001005853.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR6B2ENST00000319423.5 linkuse as main transcriptc.698G>C p.Gly233Ala missense_variant 1/1 NM_001005853.1 ENSP00000322435 P1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249492
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135380
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.0000579
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1461404
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
727056
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152148
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.0000966
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302

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 GeneticsJul 19, 2022The c.698G>C (p.G233A) alteration is located in exon 1 (coding exon 1) of the OR6B2 gene. This alteration results from a G to C substitution at nucleotide position 698, causing the glycine (G) at amino acid position 233 to be replaced by an alanine (A). 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
Benign
0.14
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.013
T
Eigen
Uncertain
0.25
Eigen_PC
Benign
0.095
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.00083
T
MetaRNN
Benign
0.29
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Uncertain
2.5
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.26
T
PROVEAN
Pathogenic
-4.7
D
REVEL
Benign
0.11
Sift
Benign
0.16
T
Sift4G
Benign
0.094
T
Polyphen
0.94
P
Vest4
0.34
MutPred
0.46
Loss of catalytic residue at P229 (P = 0.0784);
MVP
0.54
MPC
1.8
ClinPred
0.75
D
GERP RS
4.3
Varity_R
0.29
gMVP
0.19

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: rs936920628; hg19: chr2-240969149; API