1-248060763-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004687.2(OR2L3):ā€‹c.82A>Gā€‹(p.Ile28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000059 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

OR2L3
NM_001004687.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.04
Variant links:
Genes affected
OR2L3 (HGNC:15009): (olfactory receptor family 2 subfamily L member 3) 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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.031233609).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR2L3NM_001004687.2 linkuse as main transcriptc.82A>G p.Ile28Val missense_variant 2/2 ENST00000359959.4 NP_001004687.1
LOC105373275XR_949369.3 linkuse as main transcriptn.418+4373T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR2L3ENST00000359959.4 linkuse as main transcriptc.82A>G p.Ile28Val missense_variant 2/2 NM_001004687.2 ENSP00000353044 P1
OR2L3ENST00000641161.1 linkuse as main transcriptc.82A>G p.Ile28Val missense_variant 2/2 ENSP00000493424 P1
OR2L3ENST00000641649.1 linkuse as main transcriptc.82A>G p.Ile28Val missense_variant 3/3 ENSP00000493020 P1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152026
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.000478
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251404
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.0000578
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:
0.00000547
AC:
8
AN:
1461814
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000671
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152026
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.000196
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:
0.000478
Bravo
AF:
0.000110
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

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 16, 2021The c.82A>G (p.I28V) alteration is located in exon 1 (coding exon 1) of the OR2L3 gene. This alteration results from a A to G substitution at nucleotide position 82, causing the isoleucine (I) at amino acid position 28 to be replaced by a valine (V). 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
0.078
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.033
DANN
Benign
0.71
DEOGEN2
Benign
0.0039
T;T;T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0054
N
LIST_S2
Benign
0.061
.;.;T
M_CAP
Benign
0.00062
T
MetaRNN
Benign
0.031
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.47
N;N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.21
T
PROVEAN
Benign
0.090
N;.;.
REVEL
Benign
0.016
Sift
Benign
0.59
T;.;.
Sift4G
Benign
0.59
T;.;.
Polyphen
0.0020
B;B;B
Vest4
0.048
MVP
0.095
MPC
0.12
ClinPred
0.026
T
GERP RS
-0.79
Varity_R
0.033
gMVP
0.036

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: rs147120205; hg19: chr1-248224065; COSMIC: COSV63455642; API