Variant 7-144258965-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001005328.2(OR2A7):c.664T>A(p.Cys222Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000387 in 1,612,984 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 22)

Exomes 𝑓: 0.00040 ( 6 hom. )

Consequence

OR2A7
NM_001005328.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.53

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:

ARHGEF35-AS1 (HGNC:):

ARHGEF35-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2A7	NM_001005328.2 linkuse as main transcript	c.664T>A	p.Cys222Ser	missense_variant	2/2	ENST00000641841.1	NP_001005328.1	Q96R45A0A126GWD8
ARHGEF35-AS1	NR_126022.1 linkuse as main transcript	n.494-21507A>T		intron_variant
OR2A1-AS1	NR_126023.1 linkuse as main transcript	n.608-19222T>A		intron_variant
ARHGEF34P	NR_033942.1 linkuse as main transcript	n.*31T>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2A7	ENST00000641841.1 linkuse as main transcript	c.664T>A	p.Cys222Ser	missense_variant	2/2		NM_001005328.2	ENSP00000493320.1		Q96R45

Frequencies

GnomAD3 genomes

AF:

0.000297

AC:

AN:

151764

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000729

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:

0.000412

Gnomad OTH

AF:

0.000962

GnomAD3 exomes

AF:

0.000275

AC:

AN:

251224

Hom.:

AF XY:

0.000272

AC XY:

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000528

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000396

AC:

579

AN:

1461220

Hom.:

Cov.:

AF XY:

0.000393

AC XY:

286

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000180

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:

0.000496

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000297

AC:

AN:

151764

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74080

show subpopulations

Gnomad4 AFR

AF:

0.0000967

Gnomad4 AMR

AF:

0.000729

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.000962

Alfa

AF:

0.000672

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000280

AC:

EpiCase

AF:

0.000655

EpiControl

AF:

0.000474

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

Oct 06, 2022

The c.664T>A (p.C222S) alteration is located in exon 1 (coding exon 1) of the OR2A7 gene. This alteration results from a T to A substitution at nucleotide position 664, causing the cysteine (C) at amino acid position 222 to be replaced by a serine (S). 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

0.11

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.67

DANN

Benign

0.33

DEOGEN2

Benign

0.0036

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.031

M_CAP

Benign

0.0046

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.2

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.17

.;N

REVEL

Benign

0.023

Sift

Benign

0.45

.;T

Sift4G

Benign

0.44

.;T

Polyphen

0.0020

B;B

Vest4

0.091

MutPred

0.37

Loss of stability (P = 0.2319);Loss of stability (P = 0.2319);

MVP

0.10

ClinPred

0.023

GERP RS

-5.5

Varity_R

0.039

gMVP

0.074

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.27

Position offset: -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