11-6785423-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001004489.3(OR2AG1):​c.386C>T​(p.Pro129Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

OR2AG1
NM_001004489.3 missense

Scores

6
6
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.88
Variant links:
Genes affected
OR2AG1 (HGNC:15142): (olfactory receptor family 2 subfamily AG member 1) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jul 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.808

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR2AG1NM_001004489.3 linkc.386C>T p.Pro129Leu missense_variant Exon 2 of 2 ENST00000641258.1 NP_001004489.1 Q9H205A0A126GVD0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR2AG1ENST00000641258.1 linkc.386C>T p.Pro129Leu missense_variant Exon 2 of 2 NM_001004489.3 ENSP00000493074.1 Q9H205
OR2AG1ENST00000641344.1 linkn.837+21C>T intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
250990
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135618
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000150
AC:
22
AN:
1461862
Hom.:
0
Cov.:
37
AF XY:
0.00000963
AC XY:
7
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.000508
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152298
Hom.:
0
Cov.:
32
AF XY:
0.0000806
AC XY:
6
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.000131
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
Bravo
AF:
0.000117
ExAC
AF:
0.0000247
AC:
3
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 17, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.386C>T (p.P129L) alteration is located in exon 1 (coding exon 1) of the OR2AG1 gene. This alteration results from a C to T substitution at nucleotide position 386, causing the proline (P) at amino acid position 129 to be replaced by a leucine (L). 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
0.50
BayesDel_addAF
Benign
-0.0049
T
BayesDel_noAF
Uncertain
0.050
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.10
T;T
Eigen
Pathogenic
0.73
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.95
.;D
M_CAP
Benign
0.037
D
MetaRNN
Pathogenic
0.81
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.1
M;M
PrimateAI
Benign
0.32
T
PROVEAN
Pathogenic
-9.7
.;D
REVEL
Uncertain
0.39
Sift
Pathogenic
0.0
.;D
Polyphen
1.0
D;D
Vest4
0.91
MutPred
0.66
Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP
0.53
MPC
0.24
ClinPred
1.0
D
GERP RS
3.9
Varity_R
0.59
gMVP
0.28

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: rs776088768; hg19: chr11-6806654; API