1-247896410-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001001957.2(OR2W3):c.824T>C(p.Met275Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,612,292 control chromosomes in the GnomAD database, including 322,623 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M275I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.55 ( 24218 hom., cov: 30)

Exomes 𝑓: 0.63 ( 298405 hom. )

Consequence

OR2W3
NM_001001957.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.260

Publications

34 publications found

Variant links:

Genes affected

OR2W3 (HGNC:15021): (olfactory receptor family 2 subfamily W 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]

OR2W3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.0057003E-6).

BP6

Variant 1-247896410-T-C is Benign according to our data. Variant chr1-247896410-T-C is described in ClinVar as Benign. ClinVar VariationId is 1582349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2W3	NM_001001957.2 link	c.824T>C	p.Met275Thr	missense_variant	Exon 1 of 1	ENST00000360358.3	NP_001001957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2W3	ENST00000360358.3 link	c.824T>C	p.Met275Thr	missense_variant	Exon 1 of 1	6	NM_001001957.2	ENSP00000353516.3

Frequencies

GnomAD3 genomes

AF:

0.549

AC:

83036

AN:

151290

Hom.:

24222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.605

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.662

Gnomad EAS

AF:

0.576

Gnomad SAS

AF:

0.500

Gnomad FIN

AF:

0.674

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.660

Gnomad OTH

AF:

0.580

GnomAD2 exomes

AF:

0.582

AC:

146370

AN:

251350

AF XY:

0.589

show subpopulations

Gnomad AFR exome

AF:

0.338

Gnomad AMR exome

AF:

0.425

Gnomad ASJ exome

AF:

0.666

Gnomad EAS exome

AF:

0.579

Gnomad FIN exome

AF:

0.678

Gnomad NFE exome

AF:

0.661

Gnomad OTH exome

AF:

0.617

GnomAD4 exome

AF:

0.634

AC:

926761

AN:

1460882

Hom.:

298405

Cov.:

AF XY:

0.632

AC XY:

459314

AN XY:

726830

show subpopulations

African (AFR)

AF:

0.342

AC:

11460

AN:

33462

American (AMR)

AF:

0.431

AC:

19286

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.663

AC:

17319

AN:

26126

East Asian (EAS)

AF:

0.540

AC:

21427

AN:

39692

South Asian (SAS)

AF:

0.498

AC:

42982

AN:

86244

European-Finnish (FIN)

AF:

0.679

AC:

36251

AN:

53414

Middle Eastern (MID)

AF:

0.643

AC:

3708

AN:

5764

European-Non Finnish (NFE)

AF:

0.663

AC:

736923

AN:

1111108

Other (OTH)

AF:

0.620

AC:

37405

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

17716

35432

53148

70864

88580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18980

37960

56940

75920

94900

<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:

0.548

AC:

83044

AN:

151410

Hom.:

24218

Cov.:

AF XY:

0.546

AC XY:

40392

AN XY:

73956

show subpopulations

African (AFR)

AF:

0.346

AC:

14322

AN:

41354

American (AMR)

AF:

0.488

AC:

7432

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.662

AC:

2293

AN:

3464

East Asian (EAS)

AF:

0.577

AC:

2946

AN:

5110

South Asian (SAS)

AF:

0.500

AC:

2392

AN:

4788

European-Finnish (FIN)

AF:

0.674

AC:

7052

AN:

10462

Middle Eastern (MID)

AF:

0.653

AC:

192

AN:

294

European-Non Finnish (NFE)

AF:

0.660

AC:

44658

AN:

67712

Other (OTH)

AF:

0.580

AC:

1214

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1763

3525

5288

7050

8813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

706

1412

2118

2824

3530

<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:

0.620

Hom.:

56947

Bravo

AF:

0.529

TwinsUK

AF:

0.668

AC:

2477

ALSPAC

AF:

0.659

AC:

2541

ESP6500AA

AF:

0.358

AC:

1578

ESP6500EA

AF:

0.653

AC:

5617

ExAC

AF:

0.580

AC:

70379

Asia WGS

AF:

0.529

AC:

1840

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.2

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.0027

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.12

MetaRNN

Benign

0.0000020

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-3.5

PhyloP100

0.26

PrimateAI

Benign

0.34

PROVEAN

Benign

4.1

REVEL

Benign

0.28

Sift

Benign

1.0

Sift4G

Benign

0.72

Vest4

0.021

ClinPred

0.0067

GERP RS

5.3

Varity_R

0.062

gMVP

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over