dbSNP rs115522285: OR2D3:p.Ser228Phe (chr11-6921684-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001004684.1(OR2D3):c.683C>T(p.Ser228Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00847 in 1,551,934 control chromosomes in the GnomAD database, including 78 homozygotes. 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 Benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0087 ( 73 hom. )

Consequence

OR2D3
NM_001004684.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.259

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044530034).

BP6

Variant 11-6921684-C-T is Benign according to our data. Variant chr11-6921684-C-T is described in ClinVar as Benign. ClinVar VariationId is 3257585.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004684.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2D3	NM_001004684.1	MANE Select	c.683C>T	p.Ser228Phe	missense	Exon 1 of 1	NP_001004684.1	Q8NGH3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR2D3	ENST00000317834.5	TSL:6 MANE Select	c.683C>T	p.Ser228Phe	missense	Exon 1 of 1	ENSP00000320560.3	Q8NGH3
ENSG00000283415	ENST00000637205.2	TSL:5	n.605+2814G>A		intron	N/A
ENSG00000283415	ENST00000767881.1		n.214+2814G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00596

AC:

907

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00567

AC:

1108

AN:

195436

AF XY:

0.00579

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.000833

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00321

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00633

GnomAD4 exome

AF:

0.00875

AC:

12241

AN:

1399660

Hom.:

Cov.:

AF XY:

0.00864

AC XY:

5963

AN XY:

690544

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

31332

American (AMR)

AF:

0.00260

AC:

AN:

35036

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

21386

East Asian (EAS)

AF:

0.00

AC:

AN:

39338

South Asian (SAS)

AF:

0.000433

AC:

AN:

73868

European-Finnish (FIN)

AF:

0.00392

AC:

199

AN:

50702

Middle Eastern (MID)

AF:

0.000554

AC:

AN:

5412

European-Non Finnish (NFE)

AF:

0.0106

AC:

11487

AN:

1084906

Other (OTH)

AF:

0.00603

AC:

348

AN:

57680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

713

1426

2140

2853

3566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

430

860

1290

1720

2150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00596

AC:

907

AN:

152274

Hom.:

Cov.:

AF XY:

0.00549

AC XY:

409

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

41566

American (AMR)

AF:

0.00320

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00166

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00377

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0106

AC:

722

AN:

68022

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

129

172

215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00859

Hom.:

Bravo

AF:

0.00568

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00989

AC:

ExAC

AF:

0.00603

AC:

729

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.011

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

-0.26

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.057

Sift

Benign

0.46

Sift4G

Benign

0.75

Polyphen

0.014

Vest4

0.11

MVP

0.21

MPC

0.025

ClinPred

0.0068

GERP RS

3.3

Varity_R

0.19

gMVP

0.32

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over