5-181155604-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2V2	NM_206880.2	c.662A>G	p.His221Arg	missense_variant	Exon 2 of 2	ENST00000641492.1	NP_996763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2V2	ENST00000641492.1	c.662A>G	p.His221Arg	missense_variant	Exon 2 of 2		NM_206880.2	ENSP00000493207.1
OR2V2	ENST00000641791.1	c.662A>G	p.His221Arg	missense_variant	Exon 3 of 3			ENSP00000493017.1

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

GnomAD3 exomes AF: 0.598 AC: 150289 AN: 251482 Hom.: 46274 AF XY: 0.591 AC XY: 80361 AN XY: 135916

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 SAS exome AF: 0.636

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

Gnomad4 AFR exome AF: 0.797

Gnomad4 AMR exome AF: 0.751

Gnomad4 ASJ exome AF: 0.531

Gnomad4 EAS exome AF: 0.594

Gnomad4 SAS exome AF: 0.638

Gnomad4 FIN exome AF: 0.547

Gnomad4 NFE exome AF: 0.537

Gnomad4 OTH exome AF: 0.566

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

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.638

Alfa AF: 0.556 Hom.: 57918

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 v4.3

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;T;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;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.35	N;N;N
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;B;B
Vest4		0.0030
MPC		0.086
ClinPred		0.0020	T
GERP RS		0.49
Varity_R		0.038
gMVP		0.12

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

Publications

LitVar

Other links and lift over

dbSNP: rs2546423; hg19: chr5-180582604; COSMIC: COSV60314637;