11-6921743-G-A

Position:

chr11-6921743-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.742G>A(p.Glu248Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000208 in 1,536,360 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

OR2D3
NM_001004684.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.257

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]

OR2D3 links:

ENSG00000283415 (HGNC:):

ENSG00000283415 links:

Genome browser will be placed here

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=0.10430431).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2D3	NM_001004684.1 linkuse as main transcript	c.742G>A	p.Glu248Lys	missense_variant	1/1	ENST00000317834.5	NP_001004684.1	Q8NGH3
LOC107984019	XR_001748111.2 linkuse as main transcript	n.931+2755C>T		intron_variant
LOC107984019	XR_001748112.3 linkuse as main transcript	n.1466+2755C>T		intron_variant
LOC107984019	XR_007062575.1 linkuse as main transcript	n.980+2755C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2D3	ENST00000317834.5 linkuse as main transcript	c.742G>A	p.Glu248Lys	missense_variant	1/1	6	NM_001004684.1	ENSP00000320560.3		Q8NGH3
ENSG00000283415	ENST00000637205.2 linkuse as main transcript	n.605+2755C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000539

AC:

AN:

185562

Hom.:

AF XY:

0.0000103

AC XY:

AN XY:

97452

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000112

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000217

AC:

AN:

1384202

Hom.:

Cov.:

AF XY:

0.0000176

AC XY:

AN XY:

680906

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:

0.0000251

Gnomad4 OTH exome

AF:

0.0000526

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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 submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.742G>A (p.E248K) 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 742, causing the glutamic acid (E) at amino acid position 248 to be replaced by a lysine (K). 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

0.079

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0061

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.82

M_CAP

Benign

0.0029

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.59

PrimateAI

Benign

0.22

PROVEAN

Benign

-2.0

REVEL

Benign

0.070

Sift

Benign

0.041

Sift4G

Benign

0.15

Polyphen

0.16

Vest4

0.23

MutPred

0.50

Gain of MoRF binding (P = 0.0253);

MVP

0.29

MPC

0.031

ClinPred

0.15

GERP RS

3.1

Varity_R

0.18

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over