1-248180551-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001004688.2(OR2M2):​c.566G>A​(p.Cys189Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,613,744 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

OR2M2
NM_001004688.2 missense

Scores

5
2
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.92
Variant links:
Genes affected
OR2M2 (HGNC:8268): (olfactory receptor family 2 subfamily M 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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR2M2NM_001004688.2 linkuse as main transcriptc.566G>A p.Cys189Tyr missense_variant 2/2 ENST00000641836.1 NP_001004688.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR2M2ENST00000641836.1 linkuse as main transcriptc.566G>A p.Cys189Tyr missense_variant 2/2 NM_001004688.2 ENSP00000493201 P1
OR2M2ENST00000641211.1 linkuse as main transcriptc.566G>A p.Cys189Tyr missense_variant 3/3 ENSP00000492974 P1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152126
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.000191
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000757
AC:
19
AN:
251128
Hom.:
0
AF XY:
0.0000958
AC XY:
13
AN XY:
135712
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.000168
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000154
AC:
225
AN:
1461618
Hom.:
1
Cov.:
72
AF XY:
0.000144
AC XY:
105
AN XY:
727124
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.000199
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152126
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.000191
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000123
Hom.:
0
Bravo
AF:
0.000110
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000988
AC:
12
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

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 GeneticsDec 05, 2022The c.566G>A (p.C189Y) alteration is located in exon 1 (coding exon 1) of the OR2M2 gene. This alteration results from a G to A substitution at nucleotide position 566, causing the cysteine (C) at amino acid position 189 to be replaced by a tyrosine (Y). 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
0.65
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
22
DANN
Benign
0.88
DEOGEN2
Benign
0.032
T;T;T
Eigen
Benign
0.085
Eigen_PC
Benign
-0.28
FATHMM_MKL
Benign
0.31
N
LIST_S2
Uncertain
0.90
.;.;D
M_CAP
Benign
0.00092
T
MetaRNN
Uncertain
0.71
D;D;D
MetaSVM
Benign
-0.92
T
MutationAssessor
Pathogenic
3.9
H;H;H
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.32
T
PROVEAN
Pathogenic
-11
.;.;D
REVEL
Benign
0.11
Sift
Pathogenic
0.0
.;.;D
Sift4G
Pathogenic
0.0
.;.;D
Polyphen
0.99
D;D;D
Vest4
0.14
MVP
0.30
MPC
0.68
ClinPred
0.91
D
GERP RS
-0.88
Varity_R
0.77
gMVP
0.10

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: rs142105773; hg19: chr1-248343853; COSMIC: COSV62898518; API