Variant 2-240029883-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001005853.1(OR6B2):c.547C>T(p.Pro183Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR6B2
NM_001005853.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68

Variant links:

Genes affected

OR6B2 (HGNC:15041): (olfactory receptor family 6 subfamily B 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]

OR6B2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR6B2	NM_001005853.1 linkuse as main transcript	c.547C>T	p.Pro183Ser	missense_variant	1/1	ENST00000319423.5	NP_001005853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR6B2	ENST00000319423.5 linkuse as main transcript	c.547C>T	p.Pro183Ser	missense_variant	1/1		NM_001005853.1	ENSP00000322435	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000144

AC:

AN:

1386800

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694436

show subpopulations

Gnomad4 AFR exome

AF:

0.0000627

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:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Apr 25, 2022

The c.547C>T (p.P183S) alteration is located in exon 1 (coding exon 1) of the OR6B2 gene. This alteration results from a C to T substitution at nucleotide position 547, causing the proline (P) at amino acid position 183 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.21

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0027

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.36

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-8.0

REVEL

Benign

0.11

Sift

Uncertain

0.017

Sift4G

Uncertain

0.039

Polyphen

1.0

Vest4

0.50

MutPred

0.48

Loss of methylation at K186 (P = 0.0818);

MVP

0.38

MPC

1.7

ClinPred

1.0

GERP RS

4.4

Varity_R

0.77

gMVP

0.28

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