Variant chr1-248453350-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004136.2(OR2T2):c.553G>A(p.Val185Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 149,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000031 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR2T2
NM_001004136.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.15

Variant links:

Genes affected

OR2T2 (HGNC:14725): (olfactory receptor family 2 subfamily T member 2) 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]

OR2T2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.108590186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T2	NM_001004136.2 linkuse as main transcript	c.553G>A	p.Val185Met	missense_variant	4/4	ENST00000641925.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T2	ENST00000641925.2 linkuse as main transcript	c.553G>A	p.Val185Met	missense_variant	4/4		NM_001004136.2	P1
OR2T2	ENST00000642130.1 linkuse as main transcript	c.553G>A	p.Val185Met	missense_variant	3/3			P1

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

148936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000136

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000232

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000594

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000373

AC:

AN:

241454

Hom.:

AF XY:

0.0000612

AC XY:

AN XY:

130708

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000202

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000310

AC:

AN:

1418132

Hom.:

Cov.:

AF XY:

0.0000368

AC XY:

AN XY:

707114

show subpopulations

Gnomad4 AFR exome

AF:

0.000214

Gnomad4 AMR exome

AF:

0.0000462

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000518

Gnomad4 SAS exome

AF:

0.000109

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000186

Gnomad4 OTH exome

AF:

0.0000512

GnomAD4 genome

AF:

0.000114

AC:

AN:

149052

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

72632

show subpopulations

Gnomad4 AFR

AF:

0.000221

Gnomad4 AMR

AF:

0.000136

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000464

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000594

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000144

Hom.:

ExAC

AF:

0.0000578

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 16, 2024

The c.553G>A (p.V185M) alteration is located in exon 1 (coding exon 1) of the OR2T2 gene. This alteration results from a G to A substitution at nucleotide position 553, causing the valine (V) at amino acid position 185 to be replaced by a methionine (M). 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

-0.43

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.028

M_CAP

Benign

0.0031

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.2

L;L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.57

.;.;N

REVEL

Benign

0.17

Sift

Benign

0.16

.;.;T

Sift4G

Benign

0.32

.;.;T

Polyphen

1.0

D;D;D

Vest4

0.41

MutPred

0.46

Loss of ubiquitination at K187 (P = 0.1704);Loss of ubiquitination at K187 (P = 0.1704);Loss of ubiquitination at K187 (P = 0.1704);

MVP

0.56

MPC

2.7

ClinPred

0.32

GERP RS

2.7

Varity_R

0.047

gMVP

0.15

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