rs2048367090

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012352.3(OR1A2):​c.206T>A​(p.Val69Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000349 in 1,434,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V69A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

OR1A2
NM_012352.3 missense

Scores

2
3
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.158
Variant links:
Genes affected
OR1A2 (HGNC:8180): (olfactory receptor family 1 subfamily A 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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40600756).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR1A2NM_012352.3 linkc.206T>A p.Val69Asp missense_variant Exon 1 of 1 ENST00000381951.1 NP_036484.1 Q9Y585A0A126GVH4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR1A2ENST00000381951.1 linkc.206T>A p.Val69Asp missense_variant Exon 1 of 1 6 NM_012352.3 ENSP00000371377.1 Q9Y585

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000349
AC:
5
AN:
1434342
Hom.:
0
Cov.:
33
AF XY:
0.00000563
AC XY:
4
AN XY:
710410
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:
0.00000455
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Benign
-0.026
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
24
DANN
Benign
0.97
DEOGEN2
Benign
0.014
T
Eigen
Benign
0.14
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.045
N
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.41
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.3
M
PROVEAN
Pathogenic
-5.0
D
REVEL
Benign
0.14
Sift
Uncertain
0.0060
D
Sift4G
Uncertain
0.020
D
Polyphen
1.0
D
Vest4
0.47
MutPred
0.56
Loss of stability (P = 0.0298);
MVP
0.45
MPC
0.79
ClinPred
0.85
D
GERP RS
3.0
Varity_R
0.62
gMVP
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-3101018; API