rs34788973

Positions:

• chr6-27911422-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033057.2(OR2B2):​c.898G>T​(p.Ala300Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 1,613,772 control chromosomes in the GnomAD database, including 7,111 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.053 (327 hom., cov: 32)
  • Exomes 𝑓: 0.086 (6784 hom.)
• Consequence: OR2B2 NM_033057.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

Genes affected

OR2B2 (HGNC:13966): (olfactory receptor family 2 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019125342).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2B2	NM_033057.2	c.898G>T	p.Ala300Ser	missense_variant	1/1	ENST00000303324.4	NP_149046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2B2	ENST00000303324.4	c.898G>T	p.Ala300Ser	missense_variant	1/1		NM_033057.2	ENSP00000304419	P1

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8112 AN: 152110 Hom.: 327 Cov.: 32

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0259

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.0397

GnomAD3 exomes AF: 0.0477 AC: 11992 AN: 251214 Hom.: 483 AF XY: 0.0474 AC XY: 6433 AN XY: 135780

Gnomad AFR exome AF: 0.0280

Gnomad AMR exome AF: 0.0202

Gnomad ASJ exome AF: 0.0227

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000523

Gnomad FIN exome AF: 0.0392

Gnomad NFE exome AF: 0.0833

Gnomad OTH exome AF: 0.0462

GnomAD4 exome AF: 0.0860 AC: 125740 AN: 1461544 Hom.: 6784 Cov.: 32 AF XY: 0.0826 AC XY: 60082 AN XY: 727098

Gnomad4 AFR exome AF: 0.0240

Gnomad4 AMR exome AF: 0.0203

Gnomad4 ASJ exome AF: 0.0241

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000557

Gnomad4 FIN exome AF: 0.0404

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.0697

GnomAD4 genome AF: 0.0533 AC: 8112 AN: 152228 Hom.: 327 Cov.: 32 AF XY: 0.0483 AC XY: 3596 AN XY: 74440

Gnomad4 AFR AF: 0.0258

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.0398

Gnomad4 NFE AF: 0.0874

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0787 Hom.: 735

Bravo AF: 0.0515

TwinsUK AF: 0.125 AC: 462

ALSPAC AF: 0.111 AC: 426

ESP6500AA AF: 0.0361 AC: 159

ESP6500EA AF: 0.0876 AC: 753

ExAC AF: 0.0482 AC: 5850

Asia WGS AF: 0.00606 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.013
Eigen_PC	Benign	-0.064
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.073
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.010	D
Polyphen		0.97	D
Vest4		0.084
MPC		0.20
ClinPred		0.034	T
GERP RS		3.6
Varity_R		0.30
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs34788973; hg19: chr6-27879200;