Variant 1-248559487-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004694.3(OR2T29):c.5C>A(p.Ala2Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0033 ( 0 hom., cov: 24)

Exomes 𝑓: 0.0056 ( 72 hom. )

Failed GnomAD Quality Control

Consequence

OR2T29
NM_001004694.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.335

Variant links:

Genes affected

OR2T29 (HGNC:31253): (olfactory receptor family 2 subfamily T member 29) 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]

OR2T29 links:

ENSG00000224521 (HGNC:):

ENSG00000224521 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0480178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2T29	NM_001004694.3 linkuse as main transcript	c.5C>A	p.Ala2Asp	missense_variant	2/2	ENST00000641069.1	NP_001004694.2	Q8NH02

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR2T29	ENST00000641069.1 linkuse as main transcript	c.5C>A	p.Ala2Asp	missense_variant	2/2		NM_001004694.3	ENSP00000492895.1	Q8NH02
OR2T29	ENST00000328570.6 linkuse as main transcript	c.5C>A	p.Ala2Asp	missense_variant	1/1	6		ENSP00000331774.3	Q8NH02
ENSG00000224521	ENST00000438623.1 linkuse as main transcript	n.92-3113G>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

431

AN:

128728

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000199

Gnomad AMI

AF:

0.00270

Gnomad AMR

AF:

0.00617

Gnomad ASJ

AF:

0.00269

Gnomad EAS

AF:

0.0145

Gnomad SAS

AF:

0.00712

Gnomad FIN

AF:

0.00825

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00348

Gnomad OTH

AF:

0.00364

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250042

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135160

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:

0.00

Gnomad FIN exome

AF:

0.0000934

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00557

AC:

7615

AN:

1367732

Hom.:

Cov.:

AF XY:

0.00610

AC XY:

4125

AN XY:

676140

show subpopulations

Gnomad4 AFR exome

AF:

0.000332

Gnomad4 AMR exome

AF:

0.0171

Gnomad4 ASJ exome

AF:

0.00644

Gnomad4 EAS exome

AF:

0.0580

Gnomad4 SAS exome

AF:

0.0178

Gnomad4 FIN exome

AF:

0.00909

Gnomad4 NFE exome

AF:

0.00286

Gnomad4 OTH exome

AF:

0.00680

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00334

AC:

430

AN:

128846

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

212

AN XY:

61966

show subpopulations

Gnomad4 AFR

AF:

0.000198

Gnomad4 AMR

AF:

0.00617

Gnomad4 ASJ

AF:

0.00269

Gnomad4 EAS

AF:

0.0146

Gnomad4 SAS

AF:

0.00682

Gnomad4 FIN

AF:

0.00825

Gnomad4 NFE

AF:

0.00348

Gnomad4 OTH

AF:

0.00360

Alfa

AF:

0.00563

Hom.:

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

Aug 30, 2021

The c.5C>A (p.A2D) alteration is located in exon 1 (coding exon 1) of the OR2T29 gene. This alteration results from a C to A substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 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

0.068

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.1

DANN

Benign

0.82

DEOGEN2

Benign

0.0026

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00039

LIST_S2

Benign

0.24

.;T

M_CAP

Benign

0.00087

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.26

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.84

.;N

REVEL

Benign

0.017

Sift

Benign

1.0

.;T

Sift4G

Benign

0.59

.;T

Vest4

0.098

MVP

0.49

MPC

2.5

ClinPred

0.031

GERP RS

1.1

Varity_R

0.044

gMVP

0.039

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

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