Genetic Variant OR2T8:p.Phe100Val (chr1-247921315-T-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.298T>G(p.Phe100Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 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. F100I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 10)

Exomes 𝑓: 0.0000013 ( 0 hom. )

Consequence

OR2T8
NM_001005522.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.46

Publications

0 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:

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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=0.18962517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2T8	NM_001005522.2 link	c.298T>G	p.Phe100Val	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.298T>G	p.Phe100Val	missense_variant	Exon 2 of 2		NM_001005522.2	ENSP00000493286.1		A6NH00

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000134

AC:

AN:

744940

Hom.:

Cov.:

AF XY:

0.00000262

AC XY:

AN XY:

382374

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

20744

American (AMR)

AF:

0.0000334

AC:

AN:

29954

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18052

East Asian (EAS)

AF:

0.00

AC:

AN:

32996

South Asian (SAS)

AF:

0.00

AC:

AN:

55356

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45646

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2560

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

503404

Other (OTH)

AF:

0.00

AC:

AN:

36228

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.023

T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.69

.;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.6

H;H

PhyloP100

2.5

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-5.5

.;D

REVEL

Benign

0.10

Sift

Uncertain

0.0080

.;D

Sift4G

Uncertain

0.010

.;D

Polyphen

0.26

B;B

Vest4

0.37

MutPred

0.41

Gain of catalytic residue at F100 (P = 0.0797);Gain of catalytic residue at F100 (P = 0.0797);

MVP

0.64

ClinPred

0.74

GERP RS

1.3

Varity_R

0.62

gMVP

0.16

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over