Variant chr1-247921712-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005522.2(OR2T8):c.695G>A(p.Arg232His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000324 in 1,573,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R232C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000077 ( 0 hom., cov: 18)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

OR2T8
NM_001005522.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01471588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T8	NM_001005522.2 linkuse as main transcript	c.695G>A	p.Arg232His	missense_variant	2/2	ENST00000641945.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T8	ENST00000641945.2 linkuse as main transcript	c.695G>A	p.Arg232His	missense_variant	2/2		NM_001005522.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0000774

AC:

AN:

142084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000742

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00102

Gnomad SAS

AF:

0.000239

Gnomad FIN

AF:

0.000106

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000125

AC:

AN:

224148

Hom.:

AF XY:

0.0000987

AC XY:

AN XY:

121538

show subpopulations

Gnomad AFR exome

AF:

0.0000728

Gnomad AMR exome

AF:

0.0000934

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00117

Gnomad SAS exome

AF:

0.0000689

Gnomad FIN exome

AF:

0.0000502

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000178

GnomAD4 exome

AF:

0.0000280

AC:

AN:

1431078

Hom.:

Cov.:

AF XY:

0.0000239

AC XY:

AN XY:

712128

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000656

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000774

AC:

AN:

142084

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

68554

show subpopulations

Gnomad4 AFR

AF:

0.0000772

Gnomad4 AMR

AF:

0.0000742

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00102

Gnomad4 SAS

AF:

0.000239

Gnomad4 FIN

AF:

0.000106

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000128

ESP6500AA

AF:

0.000243

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000108

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.695G>A (p.R232H) alteration is located in exon 1 (coding exon 1) of the OR2T8 gene. This alteration results from a G to A substitution at nucleotide position 695, causing the arginine (R) at amino acid position 232 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.84

.;T

M_CAP

Benign

0.00081

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-3.0

.;D

REVEL

Benign

0.060

Sift

Benign

0.059

.;T

Sift4G

Uncertain

0.051

.;T

Polyphen

0.21

B;B

Vest4

0.15

MVP

0.26

ClinPred

0.046

GERP RS

1.5

Varity_R

0.070

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over