1-247949404-A-G

Variant summary

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

The NM_001001963.1(OR2L8):ā€‹c.547A>Gā€‹(p.Met183Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000039 ( 0 hom., cov: 33)
Exomes š‘“: 0.000037 ( 0 hom. )

Consequence

OR2L8
NM_001001963.1 missense

Scores

15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.77
Variant links:
Genes affected
OR2L8 (HGNC:15014): (olfactory receptor family 2 subfamily L 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

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=0.051074177).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR2L8NM_001001963.1 linkuse as main transcriptc.547A>G p.Met183Val missense_variant 1/1 ENST00000623922.1
OR2L13NM_001304535.3 linkuse as main transcriptc.-19+12020A>G intron_variant
OR2L13NM_175911.5 linkuse as main transcriptc.-144+12020A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR2L8ENST00000623922.1 linkuse as main transcriptc.547A>G p.Met183Val missense_variant 1/1 NM_001001963.1 P1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152180
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000716
AC:
18
AN:
251230
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135768
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000792
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000369
AC:
54
AN:
1461848
Hom.:
0
Cov.:
40
AF XY:
0.0000275
AC XY:
20
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000333
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152180
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000577
AC:
7

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 GeneticsNov 29, 2023The c.547A>G (p.M183V) alteration is located in exon 1 (coding exon 1) of the OR2L8 gene. This alteration results from a A to G substitution at nucleotide position 547, causing the methionine (M) at amino acid position 183 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
0.092
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
14
DANN
Benign
0.73
DEOGEN2
Benign
0.0068
T
Eigen
Benign
-0.95
Eigen_PC
Benign
-0.93
FATHMM_MKL
Benign
0.010
N
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.00068
T
MetaRNN
Benign
0.051
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.91
N
MutationTaster
Benign
0.99
N;N
PrimateAI
Benign
0.18
T
Polyphen
0.19
B
MutPred
0.44
Gain of catalytic residue at M183 (P = 0.0405);
ClinPred
0.059
T
GERP RS
0.31
Varity_R
0.083
gMVP
0.11

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs753981987; hg19: chr1-248112706; API