11-6921032-A-G

Variant names:

• chr11-6921032-A-G
• rs200833854
• NM_001004684.1:c.31A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004684.1(OR2D3):​c.31A>G​(p.Lys11Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,594,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: OR2D3 NM_001004684.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.238
• Publications: 2 publications found

Genes affected

OR2D3 (HGNC:15146): (olfactory receptor family 2 subfamily D 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]

ENSG00000283415 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02219227).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004684.1. 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
	OR2D3	NM_001004684.1	MANE Select	c.31A>G	p.Lys11Glu	missense	Exon 1 of 1	NP_001004684.1	Q8NGH3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2D3	ENST00000317834.5	TSL:6 MANE Select	c.31A>G	p.Lys11Glu	missense	Exon 1 of 1	ENSP00000320560.3	Q8NGH3
	ENSG00000283415	ENST00000637205.2	TSL:5	n.605+3466T>C		intron	N/A
	ENSG00000283415	ENST00000767881.1		n.214+3466T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000299 AC: 7 AN: 234474 AF XY: 0.0000475

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000339

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000104 AC: 15 AN: 1442652 Hom.: 0 Cov.: 30 AF XY: 0.0000140 AC XY: 10 AN XY: 716510

African (AFR) AF: 0.00 AC: 0 AN: 32372

American (AMR) AF: 0.00 AC: 0 AN: 40946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24980

East Asian (EAS) AF: 0.000177 AC: 7 AN: 39588

South Asian (SAS) AF: 0.0000244 AC: 2 AN: 82078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.00000543 AC: 6 AN: 1104560

Other (OTH) AF: 0.00 AC: 0 AN: 59540

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2 AN XY: 74506

African (AFR) AF: 0.00 AC: 0 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15306

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

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.00000824 AC: 1

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	Benign	0.080
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.4
DANN	Benign	0.87
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.24
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.061
Sift	Benign	0.21	T
Sift4G	Benign	0.90	T
Polyphen		0.0010	B
Vest4		0.15
MVP		0.18
MPC		0.025
ClinPred		0.022	T
GERP RS		-2.3
PromoterAI		0.0049	Neutral
Varity_R		0.036
gMVP		0.095
Mutation Taster		=98/2	polymorphism

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: rs200833854; hg19: chr11-6942263;