1-248650078-C-A

Position:

chr1-248650078-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001001824.2(OR2T27):c.807G>T(p.Glu269Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000317 in 1,573,434 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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. E269A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00035 ( 4 hom., cov: 26)

Exomes 𝑓: 0.00031 ( 30 hom. )

Consequence

OR2T27
NM_001001824.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.66

Variant links:

Genes affected

OR2T27 (HGNC:31252): (olfactory receptor family 2 subfamily T member 27) 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]

OR2T27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044091344).

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2T27	NM_001001824.2 link	c.807G>T	p.Glu269Asp	missense_variant	2/2	ENST00000460972.4	NP_001001824.1	Q8NH04
OR2T27	NM_001386060.1 link	c.807G>T	p.Glu269Asp	missense_variant	3/3		NP_001372989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2T27	ENST00000460972.4 link	c.807G>T	p.Glu269Asp	missense_variant	2/2	6	NM_001001824.2	ENSP00000493412.1		Q8NH04
OR2T27	ENST00000641652.1 link	c.807G>T	p.Glu269Asp	missense_variant	3/3			ENSP00000493434.1		Q8NH04

Frequencies

GnomAD3 genomes

AF:

0.000353

AC:

AN:

144376

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000479

Gnomad ASJ

AF:

0.00881

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000167

Gnomad OTH

AF:

0.00100

GnomAD3 exomes

AF:

0.000359

AC:

AN:

245428

Hom.:

AF XY:

0.000331

AC XY:

AN XY:

132778

show subpopulations

Gnomad AFR exome

AF:

0.0000644

Gnomad AMR exome

AF:

0.000237

Gnomad ASJ exome

AF:

0.00512

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000207

Gnomad OTH exome

AF:

0.000831

GnomAD4 exome

AF:

0.000313

AC:

447

AN:

1429058

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

201

AN XY:

711450

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

Gnomad4 AMR exome

AF:

0.000525

Gnomad4 ASJ exome

AF:

0.00692

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.0000356

Gnomad4 FIN exome

AF:

0.0000388

Gnomad4 NFE exome

AF:

0.000176

Gnomad4 OTH exome

AF:

0.000692

GnomAD4 genome

AF:

0.000353

AC:

AN:

144376

Hom.:

Cov.:

AF XY:

0.000485

AC XY:

AN XY:

70162

show subpopulations

Gnomad4 AFR

AF:

0.0000260

Gnomad4 AMR

AF:

0.000479

Gnomad4 ASJ

AF:

0.00881

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000167

Gnomad4 OTH

AF:

0.00100

Alfa

AF:

0.00106

Hom.:

ExAC

AF:

0.000450

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000301

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

Dec 06, 2022

The c.807G>T (p.E269D) alteration is located in exon 1 (coding exon 1) of the OR2T27 gene. This alteration results from a G to T substitution at nucleotide position 807, causing the glutamic acid (E) at amino acid position 269 to be replaced by an aspartic acid (D). 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

0.14

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0038

T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.16

.;.;T

M_CAP

Benign

0.00099

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.6

.;.;N

REVEL

Benign

0.013

Sift

Benign

0.14

.;.;T

Sift4G

Benign

0.40

.;.;T

Polyphen

0.044

B;B;B

Vest4

0.070

MutPred

0.29

Loss of ubiquitination at K272 (P = 0.1055);Loss of ubiquitination at K272 (P = 0.1055);Loss of ubiquitination at K272 (P = 0.1055);

MVP

0.28

MPC

0.45

ClinPred

0.017

GERP RS

0.29

Varity_R

0.11

gMVP

0.067

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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