Genetic Variant OR2G6:p.Met92Arg (chr1-248521921-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001013355.2(OR2G6):c.275T>G(p.Met92Arg) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR2G6
NM_001013355.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.42

Variant links:

Genes affected

OR2G6 (HGNC:27019): (olfactory receptor family 2 subfamily G member 6) 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]

OR2G6 links:

LOC105373277 (HGNC:):

LOC105373277 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2G6	NM_001013355.2 link	c.275T>G	p.Met92Arg	missense_variant	Exon 2 of 2	ENST00000641804.1	NP_001013373.1	Q5TZ20A0A126GW53
LOC105373277	XR_002958498.2 link	n.104+14760A>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2G6	ENST00000641804.1 link	c.275T>G	p.Met92Arg	missense_variant	Exon 2 of 2		NM_001013355.2	ENSP00000493355.1		Q5TZ20
OR2G6	ENST00000641501.1 link	c.275T>G	p.Met92Arg	missense_variant	Exon 2 of 2			ENSP00000492940.1		Q5TZ20

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152148

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

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:

0.000332

AC:

483

AN:

1453548

Hom.:

Cov.:

AF XY:

0.000285

AC XY:

206

AN XY:

723278

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000813

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000402

Gnomad4 OTH exome

AF:

0.000283

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000263

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000188

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

Nov 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.275T>G (p.M92R) alteration is located in exon 1 (coding exon 1) of the OR2G6 gene. This alteration results from a T to G substitution at nucleotide position 275, causing the methionine (M) at amino acid position 92 to be replaced by an arginine (R). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0059

T;T;T

Eigen

Benign

-0.087

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.95

.;.;D

M_CAP

Benign

0.0013

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.7

L;L;L

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-4.0

.;.;D

REVEL

Benign

0.21

Sift

Pathogenic

0.0

.;.;D

Sift4G

Pathogenic

0.0

.;.;D

Polyphen

0.73

P;P;P

Vest4

0.72

MutPred

0.70

Gain of disorder (P = 0.0636);Gain of disorder (P = 0.0636);Gain of disorder (P = 0.0636);

MVP

0.24

MPC

0.0095

ClinPred

0.95

GERP RS

3.7

Varity_R

0.92

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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