7-144074693-T-G

Variant summary

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

The NM_001386096.1(OR2A25):ā€‹c.474T>Gā€‹(p.His158Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,614,142 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00021 ( 0 hom., cov: 33)
Exomes š‘“: 0.000044 ( 1 hom. )

Consequence

OR2A25
NM_001386096.1 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.57
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 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=0.05084604).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR2A25NM_001386096.1 linkuse as main transcriptc.474T>G p.His158Gln missense_variant 2/2 ENST00000641663.1
OR2A25NM_001004488.2 linkuse as main transcriptc.474T>G p.His158Gln missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR2A25ENST00000641663.1 linkuse as main transcriptc.474T>G p.His158Gln missense_variant 2/2 NM_001386096.1 P1
OR2A25ENST00000408898.2 linkuse as main transcriptc.474T>G p.His158Gln missense_variant 1/1 P1
OR2A25ENST00000641441.1 linkuse as main transcriptc.474T>G p.His158Gln missense_variant 2/2 P1

Frequencies

GnomAD3 genomes
AF:
0.000197
AC:
30
AN:
152154
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000579
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000640
AC:
16
AN:
250160
Hom.:
0
AF XY:
0.0000590
AC XY:
8
AN XY:
135684
show subpopulations
Gnomad AFR exome
AF:
0.000773
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000438
AC:
64
AN:
1461870
Hom.:
1
Cov.:
52
AF XY:
0.0000550
AC XY:
40
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00111
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.000248
GnomAD4 genome
AF:
0.000210
AC:
32
AN:
152272
Hom.:
0
Cov.:
33
AF XY:
0.000228
AC XY:
17
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.000626
Gnomad4 AMR
AF:
0.000262
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:
0.000473
Alfa
AF:
0.0000953
Hom.:
0
Bravo
AF:
0.000238
ESP6500AA
AF:
0.000463
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000107
AC:
13
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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.474T>G (p.H158Q) alteration is located in exon 1 (coding exon 1) of the OR2A25 gene. This alteration results from a T to G substitution at nucleotide position 474, causing the histidine (H) at amino acid position 158 to be replaced by a glutamine (Q). 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
0.24
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
15
DANN
Benign
0.81
DEOGEN2
Benign
0.017
T;T;T
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.62
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.60
.;.;T
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.051
T;T;T
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
0.81
L;L;L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.26
T
PROVEAN
Pathogenic
-4.6
.;.;D
REVEL
Benign
0.031
Sift
Benign
0.28
.;.;T
Sift4G
Benign
0.33
.;.;T
Polyphen
1.0
D;D;D
Vest4
0.17
MutPred
0.43
Gain of catalytic residue at H158 (P = 0.1189);Gain of catalytic residue at H158 (P = 0.1189);Gain of catalytic residue at H158 (P = 0.1189);
MVP
0.21
MPC
0.087
ClinPred
0.11
T
GERP RS
2.1
Varity_R
0.24
gMVP
0.29

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: rs376429492; hg19: chr7-143771786; API