11-6892054-C-A

Variant names:

• chr11-6892054-C-A
• rs767175612
• NM_003700.1:c.447G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_003700.1(OR2D2):​c.447G>T​(p.Trp149Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,613,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: OR2D2 NM_003700.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02
• Publications: 2 publications found

Genes affected

OR2D2 (HGNC:8244): (olfactory receptor family 2 subfamily D 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]

ENSG00000283415 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.757

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003700.1. 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
	OR2D2	NM_003700.1	MANE Select	c.447G>T	p.Trp149Cys	missense	Exon 1 of 1	NP_003691.1	A0A126GVN9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2D2	ENST00000299459.3	TSL:6 MANE Select	c.447G>T	p.Trp149Cys	missense	Exon 1 of 1	ENSP00000299459.2	Q9H210
	ENSG00000283415	ENST00000637205.2	TSL:5	n.605+32444G>T		intron	N/A
	ENSG00000283415	ENST00000767881.1		n.215-27754G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.0000598 AC: 15 AN: 250676 AF XY: 0.0000591

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000973

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000623 AC: 91 AN: 1461612 Hom.: 0 Cov.: 37 AF XY: 0.0000633 AC XY: 46 AN XY: 727116

African (AFR) AF: 0.0000598 AC: 2 AN: 33458

American (AMR) AF: 0.0000448 AC: 2 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.0000630 AC: 70 AN: 1111850

Other (OTH) AF: 0.0000994 AC: 6 AN: 60378

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74398

African (AFR) AF: 0.0000241 AC: 1 AN: 41546

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67980

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.000135 Hom.: 0

Bravo AF: 0.0000793

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000577 AC: 7

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.025	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	-0.082	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.0
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-13	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.71		Loss of glycosylation at S151 (P = 0.1106)
MVP		0.81
MPC		0.082
ClinPred		0.99	D
GERP RS		5.1
PromoterAI		-0.0014	Neutral
Varity_R		0.60
gMVP		0.76
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs767175612; hg19: chr11-6913285;