11-6921655-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004684.1(OR2D3):​c.654G>A​(p.Met218Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,429,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OR2D3
NM_001004684.1 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.199
Variant links:
Genes affected
OR2D3 (HGNC:15146): (olfactory receptor family 2 subfamily D member 3) 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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07585883).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR2D3NM_001004684.1 linkuse as main transcriptc.654G>A p.Met218Ile missense_variant 1/1 ENST00000317834.5 NP_001004684.1 Q8NGH3
LOC107984019XR_001748111.2 linkuse as main transcriptn.931+2843C>T intron_variant
LOC107984019XR_001748112.3 linkuse as main transcriptn.1466+2843C>T intron_variant
LOC107984019XR_007062575.1 linkuse as main transcriptn.980+2843C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR2D3ENST00000317834.5 linkuse as main transcriptc.654G>A p.Met218Ile missense_variant 1/16 NM_001004684.1 ENSP00000320560.3 Q8NGH3
ENSG00000283415ENST00000637205.2 linkuse as main transcriptn.605+2843C>T intron_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000458
AC:
1
AN:
218448
Hom.:
0
AF XY:
0.00000860
AC XY:
1
AN XY:
116306
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:
0.0000446
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000210
AC:
3
AN:
1429060
Hom.:
0
Cov.:
35
AF XY:
0.00000424
AC XY:
3
AN XY:
708008
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000506
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378

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 GeneticsJul 26, 2024The c.654G>A (p.M218I) alteration is located in exon 1 (coding exon 1) of the OR2D3 gene. This alteration results from a G to A substitution at nucleotide position 654, causing the methionine (M) at amino acid position 218 to be replaced by an isoleucine (I). 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
0.31
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
18
DANN
Benign
0.88
DEOGEN2
Benign
0.0054
T
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.58
T
M_CAP
Benign
0.0040
T
MetaRNN
Benign
0.076
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.26
N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.17
Sift
Benign
0.51
T
Sift4G
Benign
0.57
T
Polyphen
0.022
B
Vest4
0.41
MutPred
0.25
Gain of glycosylation at S217 (P = 0.1061);
MVP
0.26
MPC
0.028
ClinPred
0.13
T
GERP RS
5.2
Varity_R
0.26
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs1310255832; hg19: chr11-6942886; API