NM_001005853.1:c.547C>T

Variant names:

• chr2-240029883-G-A
• rs991518069
• NM_001005853.1:c.547C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005853.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6B2	NM_001005853.1	MANE Select	c.547C>T	p.Pro183Ser	missense	Exon 1 of 1	NP_001005853.1	Q6IFH4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6B2	ENST00000319423.5	TSL:6 MANE Select	c.547C>T	p.Pro183Ser	missense	Exon 1 of 1	ENSP00000322435.5	Q6IFH4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000144 AC: 2 AN: 1386800 Hom.: 0 Cov.: 22 AF XY: 0.00000144 AC XY: 1 AN XY: 694436

African (AFR) AF: 0.0000627 AC: 2 AN: 31880

American (AMR) AF: 0.00 AC: 0 AN: 44520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25634

East Asian (EAS) AF: 0.00 AC: 0 AN: 39288

South Asian (SAS) AF: 0.00 AC: 0 AN: 84746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5648

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1043850

Other (OTH) AF: 0.00 AC: 0 AN: 57864

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.21	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0027	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.36	N
PhyloP100		1.7
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.11
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.039	D
Polyphen		1.0	D
Vest4		0.50
MutPred		0.48		Loss of methylation at K186 (P = 0.0818)
MVP		0.38
MPC		1.7
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.77
gMVP		0.28
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs991518069; hg19: chr2-240969300;