Variant 7-143935891-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001004685.1(OR2F2):c.659G>A(p.Arg220Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 1,613,988 control chromosomes in the GnomAD database, including 1,219 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 108 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1111 hom. )

Consequence

OR2F2
NM_001004685.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.17

Variant links:

Genes affected

OR2F2 (HGNC:8247): (olfactory receptor family 2 subfamily F 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]

OR2F2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 7-143935891-G-A is Benign according to our data. Variant chr7-143935891-G-A is described in ClinVar as [Benign]. Clinvar id is 1290091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0326 (4965/152100) while in subpopulation SAS AF= 0.048 (231/4808). AF 95% confidence interval is 0.043. There are 108 homozygotes in gnomad4. There are 2548 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 108 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2F2	NM_001004685.1 linkuse as main transcript	c.659G>A	p.Arg220Gln	missense_variant	1/1	ENST00000408955.3	NP_001004685.1	O95006

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2F2	ENST00000408955.3 linkuse as main transcript	c.659G>A	p.Arg220Gln	missense_variant	1/1	6	NM_001004685.1	ENSP00000386222.2		O95006

Frequencies

GnomAD3 genomes

AF:

0.0326

AC:

4956

AN:

151982

Hom.:

109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0257

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0176

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.0237

Gnomad SAS

AF:

0.0480

Gnomad FIN

AF:

0.0594

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0370

Gnomad OTH

AF:

0.0303

GnomAD3 exomes

AF:

0.0333

AC:

8362

AN:

251484

Hom.:

180

AF XY:

0.0352

AC XY:

4781

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0250

Gnomad AMR exome

AF:

0.0136

Gnomad ASJ exome

AF:

0.0170

Gnomad EAS exome

AF:

0.0203

Gnomad SAS exome

AF:

0.0478

Gnomad FIN exome

AF:

0.0529

Gnomad NFE exome

AF:

0.0365

Gnomad OTH exome

AF:

0.0288

GnomAD4 exome

AF:

0.0356

AC:

51993

AN:

1461888

Hom.:

1111

Cov.:

AF XY:

0.0358

AC XY:

26067

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0243

Gnomad4 AMR exome

AF:

0.0145

Gnomad4 ASJ exome

AF:

0.0176

Gnomad4 EAS exome

AF:

0.0164

Gnomad4 SAS exome

AF:

0.0471

Gnomad4 FIN exome

AF:

0.0525

Gnomad4 NFE exome

AF:

0.0364

Gnomad4 OTH exome

AF:

0.0335

GnomAD4 genome

AF:

0.0326

AC:

4965

AN:

152100

Hom.:

108

Cov.:

AF XY:

0.0343

AC XY:

2548

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0257

Gnomad4 AMR

AF:

0.0176

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.0238

Gnomad4 SAS

AF:

0.0480

Gnomad4 FIN

AF:

0.0594

Gnomad4 NFE

AF:

0.0370

Gnomad4 OTH

AF:

0.0314

Alfa

AF:

0.0329

Hom.:

Bravo

AF:

0.0283

TwinsUK

AF:

0.0345

AC:

128

ALSPAC

AF:

0.0358

AC:

138

ESP6500AA

AF:

0.0286

AC:

126

ESP6500EA

AF:

0.0349

AC:

300

ExAC

AF:

0.0339

AC:

4119

Asia WGS

AF:

0.0360

AC:

126

AN:

3478

EpiCase

AF:

0.0333

EpiControl

AF:

0.0323

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 13, 2018	This variant is associated with the following publications: (PMID: 25363768) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.0039

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0073

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.16

PROVEAN

Benign

-0.14

REVEL

Benign

0.013

Sift

Benign

0.37

Sift4G

Benign

0.31

Polyphen

0.0

Vest4

0.015

MPC

0.019

ClinPred

0.0021

GERP RS

-7.0

Varity_R

0.025

gMVP

0.096

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.74

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.74

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