1-247921136-A-G
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001005522.2(OR2T8):c.119A>G(p.Asn40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000675 in 148,086 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 (★).
Frequency
Genomes: 𝑓 0.0000068 ( 0 hom., cov: 23)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
OR2T8
NM_001005522.2 missense
NM_001005522.2 missense
Scores
3
7
9
Clinical Significance
Conservation
PhyloP100: 2.89
Publications
1 publications found
Genes affected
OR2T8 (HGNC:15020): (olfactory receptor family 2 subfamily T member 8) 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 was made for transcript
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.975
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000675 AC: 1AN: 148086Hom.: 0 Cov.: 23 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
148086
Hom.:
Cov.:
23
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000480 AC: 7AN: 1458008Hom.: 0 Cov.: 38 AF XY: 0.00000689 AC XY: 5AN XY: 725466 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
7
AN:
1458008
Hom.:
Cov.:
38
AF XY:
AC XY:
5
AN XY:
725466
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33384
American (AMR)
AF:
AC:
1
AN:
44088
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26032
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86014
European-Finnish (FIN)
AF:
AC:
0
AN:
53338
Middle Eastern (MID)
AF:
AC:
0
AN:
5744
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1109442
Other (OTH)
AF:
AC:
1
AN:
60270
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.518
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000675 AC: 1AN: 148086Hom.: 0 Cov.: 23 AF XY: 0.0000139 AC XY: 1AN XY: 71898 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
148086
Hom.:
Cov.:
23
AF XY:
AC XY:
1
AN XY:
71898
show subpopulations
African (AFR)
AF:
AC:
0
AN:
40018
American (AMR)
AF:
AC:
1
AN:
14778
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3436
East Asian (EAS)
AF:
AC:
0
AN:
5018
South Asian (SAS)
AF:
AC:
0
AN:
4406
European-Finnish (FIN)
AF:
AC:
0
AN:
10166
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67032
Other (OTH)
AF:
AC:
0
AN:
2018
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Dec 18, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.119A>G (p.N40S) alteration is located in exon 1 (coding exon 1) of the OR2T8 gene. This alteration results from a A to G substitution at nucleotide position 119, causing the asparagine (N) at amino acid position 40 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
.;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H
PhyloP100
PrimateAI
Benign
T
PROVEAN
Uncertain
.;D
REVEL
Uncertain
Sift
Uncertain
.;D
Sift4G
Pathogenic
.;D
Polyphen
D;D
Vest4
0.44
MutPred
Gain of glycosylation at S41 (P = 0.1882);Gain of glycosylation at S41 (P = 0.1882);
MVP
0.92
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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