Variant chr7-144259047-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001005328.2(OR2A7):c.582T>G(p.Asn194Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (★).

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 21)

Exomes 𝑓: 0.0030 ( 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: -0.0690

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 -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3192761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2A7	NM_001005328.2 linkuse as main transcript	c.582T>G	p.Asn194Lys	missense_variant	2/2	ENST00000641841.1	NP_001005328.1	Q96R45A0A126GWD8
ARHGEF34P	NR_033942.1 linkuse as main transcript	n.4153T>G		non_coding_transcript_exon_variant	13/13
ARHGEF35-AS1	NR_126022.1 linkuse as main transcript	n.494-21425A>C		intron_variant
OR2A1-AS1	NR_126023.1 linkuse as main transcript	n.608-19304T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2A7	ENST00000641841.1 linkuse as main transcript	c.582T>G	p.Asn194Lys	missense_variant	2/2		NM_001005328.2	ENSP00000493320.1		Q96R45

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

143812

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000253

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:

0.000107

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000307

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00296

AC:

4225

AN:

1428308

Hom.:

Cov.:

AF XY:

0.00284

AC XY:

2019

AN XY:

711968

show subpopulations

Gnomad4 AFR exome

AF:

0.00295

Gnomad4 AMR exome

AF:

0.0000675

Gnomad4 ASJ exome

AF:

0.00101

Gnomad4 EAS exome

AF:

0.000303

Gnomad4 SAS exome

AF:

0.00109

Gnomad4 FIN exome

AF:

0.0000751

Gnomad4 NFE exome

AF:

0.00356

Gnomad4 OTH exome

AF:

0.00228

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000278

AC:

AN:

143812

Hom.:

Cov.:

AF XY:

0.0000287

AC XY:

AN XY:

69702

show subpopulations

Gnomad4 AFR

AF:

0.0000253

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000107

Gnomad4 NFE

AF:

0.0000307

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

Nov 17, 2023

The c.582T>G (p.N194K) alteration is located in exon 1 (coding exon 1) of the OR2A7 gene. This alteration results from a T to G substitution at nucleotide position 582, causing the asparagine (N) at amino acid position 194 to be replaced by a lysine (K). 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

0.23

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.013

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.12

M_CAP

Benign

0.0032

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-4.5

.;D

REVEL

Benign

0.024

Sift

Uncertain

0.0030

.;D

Sift4G

Uncertain

0.052

.;T

Polyphen

1.0

D;D

Vest4

0.29

MutPred

0.54

Gain of ubiquitination at N194 (P = 0.0388);Gain of ubiquitination at N194 (P = 0.0388);

MVP

0.39

ClinPred

0.67

GERP RS

0.63

Varity_R

0.34

gMVP

0.14

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over