1-248521795-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001013355.2(OR2G6):c.149G>T(p.Cys50Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C50G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

OR2G6
NM_001013355.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.35

Publications

2 publications found

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:

ENSG00000229255 (HGNC:):

ENSG00000229255 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026936412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2G6	NM_001013355.2 link	c.149G>T	p.Cys50Phe	missense_variant	Exon 2 of 2	ENST00000641804.1	NP_001013373.1	Q5TZ20A0A126GW53
LOC105373277	XR_002958498.2 link	n.104+14886C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2G6	ENST00000641804.1 link	c.149G>T	p.Cys50Phe	missense_variant	Exon 2 of 2		NM_001013355.2	ENSP00000493355.1		Q5TZ20

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

251362

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000134

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111988

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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.149G>T (p.C50F) alteration is located in exon 1 (coding exon 1) of the OR2G6 gene. This alteration results from a G to T substitution at nucleotide position 149, causing the cysteine (C) at amino acid position 50 to be replaced by a phenylalanine (F). 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

0.073

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.43

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.0030

T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0062

LIST_S2

Benign

0.26

.;.;T

M_CAP

Benign

0.00062

MetaRNN

Benign

0.027

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.63

N;N;N

PhyloP100

-3.4

PrimateAI

Benign

0.17

PROVEAN

Benign

0.25

.;.;N

REVEL

Benign

0.0080

Sift

Benign

0.68

.;.;T

Sift4G

Benign

0.70

.;.;T

Polyphen

0.0

B;B;B

Vest4

0.069

MutPred

0.18

Gain of glycosylation at S53 (P = 0.2568);Gain of glycosylation at S53 (P = 0.2568);Gain of glycosylation at S53 (P = 0.2568);

MVP

0.072

MPC

0.0073

ClinPred

0.036

GERP RS

-3.6

Varity_R

0.058

gMVP

0.069

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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1-248521795-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over