Genetic Variant OR2T8:p.Arg92Gly (chr1-247921291-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005522.2(OR2T8):c.274C>G(p.Arg92Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R92C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000085 ( 0 hom., cov: 15)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

OR2T8
NM_001005522.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

Publications

4 publications found

Variant links:

Genes affected

OR2T8 (HGNC:15020): (olfactory receptor family 2 subfamily T member 8) 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]

OR2T8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07538745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2T8	NM_001005522.2 link	c.274C>G	p.Arg92Gly	missense_variant	Exon 2 of 2	ENST00000641945.2	NP_001005522.1	A6NH00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2T8	ENST00000641945.2 link	c.274C>G	p.Arg92Gly	missense_variant	Exon 2 of 2		NM_001005522.2	ENSP00000493286.1		A6NH00

Frequencies

GnomAD3 genomes

AF:

0.00000848

AC:

AN:

117918

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:

0.0000172

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000175

AC:

AN:

1144466

Hom.:

Cov.:

AF XY:

0.00000174

AC XY:

AN XY:

575886

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26604

American (AMR)

AF:

0.00

AC:

AN:

36064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21596

East Asian (EAS)

AF:

0.00

AC:

AN:

36024

South Asian (SAS)

AF:

0.00

AC:

AN:

69282

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3476

European-Non Finnish (NFE)

AF:

0.00000235

AC:

AN:

851826

Other (OTH)

AF:

0.00

AC:

AN:

49496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000848

AC:

AN:

117918

Hom.:

Cov.:

AF XY:

0.0000181

AC XY:

AN XY:

55238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29132

American (AMR)

AF:

0.00

AC:

AN:

10522

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3090

East Asian (EAS)

AF:

0.00

AC:

AN:

4224

South Asian (SAS)

AF:

0.00

AC:

AN:

2912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000172

AC:

AN:

58106

Other (OTH)

AF:

0.00

AC:

AN:

1478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.0

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.0041

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.56

.;T

M_CAP

Benign

0.00064

MetaRNN

Benign

0.075

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M

PhyloP100

-1.7

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.2

.;N

REVEL

Benign

0.028

Sift

Benign

0.17

.;T

Sift4G

Benign

0.065

.;T

Polyphen

0.051

B;B

Vest4

0.11

MutPred

0.57

Gain of glycosylation at S91 (P = 0.0346);Gain of glycosylation at S91 (P = 0.0346);

MVP

0.21

ClinPred

0.088

GERP RS

-1.8

Varity_R

0.12

gMVP

0.073

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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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1-247921291-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over