Variant 12-55452253-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_054105.2(OR6C2):c.40G>A(p.Gly14Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,608,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

OR6C2
NM_054105.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.25

Variant links:

Genes affected

OR6C2 (HGNC:15436): (olfactory receptor family 6 subfamily C 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]

OR6C2 links:

ENSG00000258763 (HGNC:):

ENSG00000258763 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.885

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR6C2	NM_054105.2 linkuse as main transcript	c.40G>A	p.Gly14Arg	missense_variant	2/2	ENST00000641202.1	NP_473446.1	Q9NZP2A0A126GW05
LOC124902940	XR_007063324.1 linkuse as main transcript	n.88+233C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR6C2	ENST00000641202.1 linkuse as main transcript	c.40G>A	p.Gly14Arg	missense_variant	2/2		NM_054105.2	ENSP00000493222.1		Q9NZP2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456660

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724306

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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 21, 2024

The c.40G>A (p.G14R) alteration is located in exon 1 (coding exon 1) of the OR6C2 gene. This alteration results from a G to A substitution at nucleotide position 40, causing the glycine (G) at amino acid position 14 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

Pathogenic

0.68

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

.;.;D

M_CAP

Benign

0.0027

MetaRNN

Pathogenic

0.89

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

M;M;M

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-7.2

.;.;D

REVEL

Benign

0.14

Sift

Pathogenic

0.0

.;.;D

Sift4G

Uncertain

0.023

.;.;D

Polyphen

0.99

D;D;D

Vest4

0.85

MutPred

0.74

Gain of MoRF binding (P = 0.0658);Gain of MoRF binding (P = 0.0658);Gain of MoRF binding (P = 0.0658);

MVP

0.53

MPC

0.0052

ClinPred

1.0

GERP RS

3.4

Varity_R

0.74

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