rs34788973

Variant names:

• chr6-27911422-C-A
• rs34788973
• NM_033057.2:c.898G>T

Variant summary

Our verdict is Benign. The variant received -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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OR2B2	NM_033057.2	c.898G>T	p.Ala300Ser	missense_variant	Exon 1 of 1	ENST00000303324.4	NP_149046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2B2	ENST00000303324.4	c.898G>T	p.Ala300Ser	missense_variant	Exon 1 of 1	6	NM_033057.2	ENSP00000304419.2

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

GnomAD2 exomes AF: 0.0477 AC: 11992 AN: 251214 AF XY: 0.0474

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 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

African (AFR) AF: 0.0240 AC: 803 AN: 33472

American (AMR) AF: 0.0203 AC: 909 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0241 AC: 630 AN: 26130

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39698

South Asian (SAS) AF: 0.000557 AC: 48 AN: 86218

European-Finnish (FIN) AF: 0.0404 AC: 2160 AN: 53416

Middle Eastern (MID) AF: 0.00832 AC: 48 AN: 5766

European-Non Finnish (NFE) AF: 0.105 AC: 116928 AN: 1111752

Other (OTH) AF: 0.0697 AC: 4210 AN: 60376

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

African (AFR) AF: 0.0258 AC: 1070 AN: 41528

American (AMR) AF: 0.0258 AC: 395 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.0398 AC: 422 AN: 10598

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0874 AC: 5944 AN: 68008

Other (OTH) AF: 0.0393 AC: 83 AN: 2112

Alfa AF: 0.0733 Hom.: 883

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
PhyloP100		1.6
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34788973; hg19: chr6-27879200; COSMIC: COSV107323362;