1-248180686-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004688.2(OR2M2):​c.701G>A​(p.Arg234His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,612,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

OR2M2
NM_001004688.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0490
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.070783585).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR2M2NM_001004688.2 linkuse as main transcriptc.701G>A p.Arg234His 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.701G>A p.Arg234His missense_variant 2/2 NM_001004688.2 ENSP00000493201 P1
OR2M2ENST00000641211.1 linkuse as main transcriptc.701G>A p.Arg234His missense_variant 3/3 ENSP00000492974 P1

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152124
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000145
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251012
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135662
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000158
AC:
23
AN:
1460236
Hom.:
0
Cov.:
80
AF XY:
0.00000964
AC XY:
7
AN XY:
726482
show subpopulations
Gnomad4 AFR exome
AF:
0.000150
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152124
Hom.:
0
Cov.:
33
AF XY:
0.0000807
AC XY:
6
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.000145
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:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000115
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000247
AC:
3

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 GeneticsApr 04, 2024The c.701G>A (p.R234H) 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 701, causing the arginine (R) at amino acid position 234 to be replaced by a histidine (H). 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
0.11
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
8.2
DANN
Benign
0.91
DEOGEN2
Benign
0.015
T;T;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.58
.;.;T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.071
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.1
M;M;M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.20
T
PROVEAN
Uncertain
-3.2
.;.;D
REVEL
Benign
0.12
Sift
Benign
0.053
.;.;T
Sift4G
Benign
0.061
.;.;T
Polyphen
0.058
B;B;B
Vest4
0.056
MutPred
0.52
Loss of methylation at R234 (P = 0.0085);Loss of methylation at R234 (P = 0.0085);Loss of methylation at R234 (P = 0.0085);
MVP
0.11
MPC
0.14
ClinPred
0.042
T
GERP RS
-0.10
Varity_R
0.16
gMVP
0.078

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: rs775272894; hg19: chr1-248343988; COSMIC: COSV62897939; API