chr7-144074484-A-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.265A>Gā€‹(p.Lys89Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,104 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000085 ( 0 hom., cov: 33)
Exomes š‘“: 0.000028 ( 0 hom. )

Consequence

OR2A25
NM_001386096.1 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01
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=0.05421838).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR2A25NM_001386096.1 linkuse as main transcriptc.265A>G p.Lys89Glu missense_variant 2/2 ENST00000641663.1
OR2A25NM_001004488.2 linkuse as main transcriptc.265A>G p.Lys89Glu missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR2A25ENST00000641663.1 linkuse as main transcriptc.265A>G p.Lys89Glu missense_variant 2/2 NM_001386096.1 P1
OR2A25ENST00000408898.2 linkuse as main transcriptc.265A>G p.Lys89Glu missense_variant 1/1 P1
OR2A25ENST00000641441.1 linkuse as main transcriptc.265A>G p.Lys89Glu missense_variant 2/2 P1

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152216
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000654
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000875
AC:
22
AN:
251300
Hom.:
0
AF XY:
0.0000736
AC XY:
10
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000491
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:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000280
AC:
41
AN:
1461888
Hom.:
0
Cov.:
53
AF XY:
0.0000330
AC XY:
24
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000514
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:
0.0000117
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152216
Hom.:
0
Cov.:
33
AF XY:
0.000121
AC XY:
9
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.000110
ExAC
AF:
0.0000741
AC:
9
EpiCase
AF:
0.00
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 GeneticsJun 10, 2024The c.265A>G (p.K89E) alteration is located in exon 1 (coding exon 1) of the OR2A25 gene. This alteration results from a A to G substitution at nucleotide position 265, causing the lysine (K) at amino acid position 89 to be replaced by a glutamic acid (E). 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
0.16
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
18
DANN
Benign
0.96
DEOGEN2
Benign
0.0071
T;T;T
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.73
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.59
.;.;T
M_CAP
Benign
0.0098
T
MetaRNN
Benign
0.054
T;T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Uncertain
2.5
M;M;M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.27
T
PROVEAN
Uncertain
-2.8
.;.;D
REVEL
Benign
0.10
Sift
Uncertain
0.0010
.;.;D
Sift4G
Uncertain
0.023
.;.;D
Polyphen
0.017
B;B;B
Vest4
0.18
MutPred
0.54
Loss of methylation at K89 (P = 0.0152);Loss of methylation at K89 (P = 0.0152);Loss of methylation at K89 (P = 0.0152);
MVP
0.19
MPC
0.013
ClinPred
0.099
T
GERP RS
2.5
Varity_R
0.57
gMVP
0.11

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: rs199712223; hg19: chr7-143771577; API