Variant 7-144259175-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005328.2(OR2A7):c.454G>A(p.Val152Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR2A7
NM_001005328.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.51

Variant links:

Genes affected

OR2A7 (HGNC:8234): (olfactory receptor family 2 subfamily A member 7) 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]

OR2A7 links:

ARHGEF34P (HGNC:):

ARHGEF34P links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09931484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2A7	NM_001005328.2 linkuse as main transcript	c.454G>A	p.Val152Ile	missense_variant	2/2	ENST00000641841.1	NP_001005328.1	Q96R45A0A126GWD8
ARHGEF34P	NR_033942.1 linkuse as main transcript	n.4025G>A		non_coding_transcript_exon_variant	13/13
ARHGEF35-AS1	NR_126022.1 linkuse as main transcript	n.494-21297C>T		intron_variant
OR2A1-AS1	NR_126023.1 linkuse as main transcript	n.608-19432G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2A7	ENST00000641841.1 linkuse as main transcript	c.454G>A	p.Val152Ile	missense_variant	2/2		NM_001005328.2	ENSP00000493320.1		Q96R45

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

131422

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000569

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000749

AC:

AN:

1068032

Hom.:

Cov.:

AF XY:

0.00000557

AC XY:

AN XY:

538818

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000103

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000152

AC:

AN:

131422

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

62678

show subpopulations

Gnomad4 AFR

AF:

0.0000569

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Apr 25, 2023

The c.454G>A (p.V152I) alteration is located in exon 1 (coding exon 1) of the OR2A7 gene. This alteration results from a G to A substitution at nucleotide position 454, causing the valine (V) at amino acid position 152 to be replaced by an isoleucine (I). 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

0.070

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.22

DANN

Benign

0.89

DEOGEN2

Benign

0.0015

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.038

M_CAP

Benign

0.0025

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.17

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

0.46

.;N

REVEL

Benign

0.014

Sift

Benign

0.26

.;T

Sift4G

Benign

0.27

.;T

Polyphen

0.013

B;B

Vest4

0.033

MutPred

0.42

Loss of catalytic residue at V152 (P = 0.1315);Loss of catalytic residue at V152 (P = 0.1315);

MVP

0.067

ClinPred

0.073

GERP RS

0.93

Varity_R

0.022

gMVP

0.037

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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