chr7-144074670-G-A

Variant summary

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

The NM_001386096.1(OR2A25):​c.451G>A​(p.Gly151Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,182 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

OR2A25
NM_001386096.1 missense

Scores

4
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23
Variant links:
Genes affected
OR2A25 (HGNC:19562): (olfactory receptor family 2 subfamily A member 25) 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 UniProt
OR2A25NM_001386096.1 linkuse as main transcriptc.451G>A p.Gly151Arg missense_variant 2/2 ENST00000641663.1
OR2A25NM_001004488.2 linkuse as main transcriptc.451G>A p.Gly151Arg missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR2A25ENST00000641663.1 linkuse as main transcriptc.451G>A p.Gly151Arg missense_variant 2/2 NM_001386096.1 P1
OR2A25ENST00000408898.2 linkuse as main transcriptc.451G>A p.Gly151Arg missense_variant 1/1 P1
OR2A25ENST00000641441.1 linkuse as main transcriptc.451G>A p.Gly151Arg missense_variant 2/2 P1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000200
AC:
5
AN:
250244
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135722
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:
0.0000264
Gnomad OTH exome
AF:
0.000329
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461884
Hom.:
0
Cov.:
51
AF XY:
0.0000138
AC XY:
10
AN XY:
727248
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:
0.0000144
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152298
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000247
AC:
3
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 GeneticsFeb 07, 2023The c.451G>A (p.G151R) alteration is located in exon 1 (coding exon 1) of the OR2A25 gene. This alteration results from a G to A substitution at nucleotide position 451, causing the glycine (G) at amino acid position 151 to be replaced by an arginine (R). 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
Uncertain
0.45
BayesDel_addAF
Uncertain
0.025
T
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.064
T;T;T
Eigen
Uncertain
0.38
Eigen_PC
Benign
0.14
FATHMM_MKL
Benign
0.50
N
LIST_S2
Uncertain
0.90
.;.;D
M_CAP
Benign
0.016
T
MetaRNN
Uncertain
0.61
D;D;D
MetaSVM
Benign
-0.49
T
MutationAssessor
Pathogenic
3.1
M;M;M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.31
T
PROVEAN
Pathogenic
-5.5
.;.;D
REVEL
Benign
0.26
Sift
Pathogenic
0.0
.;.;D
Sift4G
Pathogenic
0.0010
.;.;D
Polyphen
1.0
D;D;D
Vest4
0.76
MutPred
0.79
Gain of MoRF binding (P = 0.0181);Gain of MoRF binding (P = 0.0181);Gain of MoRF binding (P = 0.0181);
MVP
0.47
MPC
0.097
ClinPred
0.93
D
GERP RS
4.6
Varity_R
0.88
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs201188715; hg19: chr7-143771763; API