5-181155604-A-G

Variant names:

• chr5-181155604-A-G
• rs2546423
• NM_206880.2:c.662A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206880.2(OR2V2):​c.662A>G​(p.His221Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 1,613,848 control chromosomes in the GnomAD database, including 261,758 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.63 (30769 hom., cov: 32)
  • Exomes 𝑓: 0.56 (230989 hom.)
• Consequence: OR2V2 NM_206880.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.29
• Publications: 36 publications found

Genes affected

OR2V2 (HGNC:15341): (olfactory receptor family 2 subfamily V 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=8.705043E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206880.2. 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
	OR2V2	NM_206880.2	MANE Select	c.662A>G	p.His221Arg	missense	Exon 2 of 2	NP_996763.1	Q96R30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2V2	ENST00000641492.1	MANE Select	c.662A>G	p.His221Arg	missense	Exon 2 of 2	ENSP00000493207.1	Q96R30
	OR2V2	ENST00000641791.1		c.662A>G	p.His221Arg	missense	Exon 3 of 3	ENSP00000493017.1	Q96R30

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95255 AN: 151906 Hom.: 30719 Cov.: 32

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.634

GnomAD2 exomes AF: 0.598 AC: 150289 AN: 251482 AF XY: 0.591

Gnomad AFR exome AF: 0.787

Gnomad AMR exome AF: 0.761

Gnomad ASJ exome AF: 0.526

Gnomad EAS exome AF: 0.554

Gnomad FIN exome AF: 0.552

Gnomad NFE exome AF: 0.533

Gnomad OTH exome AF: 0.585

GnomAD4 exome AF: 0.559 AC: 816673 AN: 1461824 Hom.: 230989 Cov.: 67 AF XY: 0.560 AC XY: 407276 AN XY: 727212

African (AFR) AF: 0.797 AC: 26692 AN: 33480

American (AMR) AF: 0.751 AC: 33604 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 13871 AN: 26136

East Asian (EAS) AF: 0.594 AC: 23590 AN: 39700

South Asian (SAS) AF: 0.638 AC: 55019 AN: 86254

European-Finnish (FIN) AF: 0.547 AC: 29206 AN: 53420

Middle Eastern (MID) AF: 0.630 AC: 3636 AN: 5768

European-Non Finnish (NFE) AF: 0.537 AC: 596864 AN: 1111948

Other (OTH) AF: 0.566 AC: 34191 AN: 60394

GnomAD4 genome AF: 0.627 AC: 95372 AN: 152024 Hom.: 30769 Cov.: 32 AF XY: 0.631 AC XY: 46843 AN XY: 74292

African (AFR) AF: 0.782 AC: 32458 AN: 41498

American (AMR) AF: 0.696 AC: 10637 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1797 AN: 3472

East Asian (EAS) AF: 0.569 AC: 2938 AN: 5162

South Asian (SAS) AF: 0.614 AC: 2950 AN: 4802

European-Finnish (FIN) AF: 0.560 AC: 5906 AN: 10550

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36668 AN: 67956

Other (OTH) AF: 0.638 AC: 1344 AN: 2106

Alfa AF: 0.565 Hom.: 109833

Bravo AF: 0.645

TwinsUK AF: 0.540 AC: 2004

ALSPAC AF: 0.550 AC: 2120

ESP6500AA AF: 0.779 AC: 3431

ESP6500EA AF: 0.533 AC: 4588

ExAC AF: 0.592 AC: 71890

Asia WGS AF: 0.639 AC: 2223 AN: 3478

EpiCase AF: 0.542

EpiControl AF: 0.545

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.89	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.047
DANN	Benign	0.087
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0028	N
LIST_S2	Benign	0.034	T
MetaRNN	Benign	8.7e-7	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.35	N
PhyloP100		-3.3
PrimateAI	Benign	0.17	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.0090
Sift	Benign	1.0	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.0030
MPC		0.086
ClinPred		0.0020	T
GERP RS		0.49
Varity_R		0.038
gMVP		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2546423; hg19: chr5-180582604; COSMIC: COSV60314637;