1-247895681-T-G

Position:

• chr1-247895681-T-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001001957.2(OR2W3):​c.95T>G​(p.Leu32Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000685 in 1,614,008 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00060 (7 hom.)
• Consequence: OR2W3 NM_001001957.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 5.55

Genes affected

OR2W3 (HGNC:15021): (olfactory receptor family 2 subfamily W member 3) 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013338327).
• BP6: Variant 1-247895681-T-G is Benign according to our data. Variant chr1-247895681-T-G is described in ClinVar as [Benign]. Clinvar id is 1596160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2W3	NM_001001957.2	c.95T>G	p.Leu32Arg	missense_variant	1/1	ENST00000360358.3	NP_001001957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2W3	ENST00000360358.3	c.95T>G	p.Leu32Arg	missense_variant	1/1	6	NM_001001957.2	ENSP00000353516.3

Frequencies

GnomAD3 genomes AF: 0.00147 AC: 224 AN: 152158 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00218 AC: 548 AN: 251476 Hom.: 4 AF XY: 0.00191 AC XY: 260 AN XY: 135910

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.0138

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000924

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.000603 AC: 882 AN: 1461732 Hom.: 7 Cov.: 35 AF XY: 0.000580 AC XY: 422 AN XY: 727194

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.0147

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00189

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000468

Gnomad4 OTH exome AF: 0.000944

GnomAD4 genome AF: 0.00147 AC: 224 AN: 152276 Hom.: 2 Cov.: 31 AF XY: 0.00163 AC XY: 121 AN XY: 74450

Gnomad4 AFR AF: 0.000794

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000385 Hom.: 1

Bravo AF: 0.00196

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00180 AC: 218

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

OR2W3-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.43
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Pathogenic	4.3	H
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.87
MVP		0.71
ClinPred		1.0	D
GERP RS		4.1
Varity_R		0.84
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs148037186; hg19: chr1-248058983;