Genetic Variant OR2D2:p.Val302Ala (chr11-6891596-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003700.1(OR2D2):c.905T>C(p.Val302Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,612,832 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

OR2D2
NM_003700.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.200

Publications

4 publications found

Variant links:

Genes affected

OR2D2 (HGNC:8244): (olfactory receptor family 2 subfamily D 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]

OR2D2 links:

ENSG00000283415 (HGNC:):

ENSG00000283415 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016853273).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003700.1. 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
	OR2D2	NM_003700.1	MANE Select	c.905T>C	p.Val302Ala	missense	Exon 1 of 1	NP_003691.1	A0A126GVN9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR2D2	ENST00000299459.3	TSL:6 MANE Select	c.905T>C	p.Val302Ala	missense	Exon 1 of 1	ENSP00000299459.2	Q9H210
ENSG00000283415	ENST00000637205.2	TSL:5	n.605+32902T>C		intron	N/A
ENSG00000283415	ENST00000767881.1		n.215-27296T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000487

AC:

122

AN:

250424

AF XY:

0.000510

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000790

Gnomad NFE exome

AF:

0.000866

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00106

AC:

1553

AN:

1460598

Hom.:

Cov.:

AF XY:

0.000986

AC XY:

716

AN XY:

726488

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33410

American (AMR)

AF:

0.0000224

AC:

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86178

European-Finnish (FIN)

AF:

0.000956

AC:

AN:

53338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00131

AC:

1457

AN:

1111170

Other (OTH)

AF:

0.000597

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

148

223

297

371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.000460

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41548

American (AMR)

AF:

0.000131

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000660

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000838

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000669

Hom.:

Bravo

AF:

0.000438

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.000412

AC:

EpiCase

AF:

0.000655

EpiControl

AF:

0.000889

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.7

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0075

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.19

M_CAP

Benign

0.0039

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.95

PhyloP100

0.20

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.3

REVEL

Benign

0.12

Sift

Benign

0.31

Sift4G

Benign

0.14

Polyphen

0.0010

Vest4

0.15

MVP

0.44

MPC

0.015

ClinPred

0.016

GERP RS

5.1

Varity_R

0.14

gMVP

0.18

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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