Variant 11-6921684-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001004684.1(OR2D3):c.683C>T(p.Ser228Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00847 in 1,551,934 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0087 ( 73 hom. )

Consequence

OR2D3
NM_001004684.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.259

Variant links:

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]

OR2D3 links:

ENSG00000283415 (HGNC:):

ENSG00000283415 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044530034).

BP6

Variant 11-6921684-C-T is Benign according to our data. Variant chr11-6921684-C-T is described in ClinVar as [Benign]. Clinvar id is 3257585.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2D3	NM_001004684.1 linkuse as main transcript	c.683C>T	p.Ser228Phe	missense_variant	1/1	ENST00000317834.5	NP_001004684.1	Q8NGH3
LOC107984019	XR_001748111.2 linkuse as main transcript	n.931+2814G>A		intron_variant
LOC107984019	XR_001748112.3 linkuse as main transcript	n.1466+2814G>A		intron_variant
LOC107984019	XR_007062575.1 linkuse as main transcript	n.980+2814G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2D3	ENST00000317834.5 linkuse as main transcript	c.683C>T	p.Ser228Phe	missense_variant	1/1	6	NM_001004684.1	ENSP00000320560.3		Q8NGH3
ENSG00000283415	ENST00000637205.2 linkuse as main transcript	n.605+2814G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00596

AC:

907

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00567

AC:

1108

AN:

195436

Hom.:

AF XY:

0.00579

AC XY:

597

AN XY:

103146

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.000833

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000346

Gnomad FIN exome

AF:

0.00321

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00633

GnomAD4 exome

AF:

0.00875

AC:

12241

AN:

1399660

Hom.:

Cov.:

AF XY:

0.00864

AC XY:

5963

AN XY:

690544

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00260

Gnomad4 ASJ exome

AF:

0.00173

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000433

Gnomad4 FIN exome

AF:

0.00392

Gnomad4 NFE exome

AF:

0.0106

Gnomad4 OTH exome

AF:

0.00603

GnomAD4 genome

AF:

0.00596

AC:

907

AN:

152274

Hom.:

Cov.:

AF XY:

0.00549

AC XY:

409

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00900

Hom.:

Bravo

AF:

0.00568

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00989

AC:

ExAC

AF:

0.00603

AC:

729

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

OR2D3: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.51

DEOGEN2

Benign

0.011

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.057

Sift

Benign

0.46

Sift4G

Benign

0.75

Polyphen

0.014

Vest4

0.11

MVP

0.21

MPC

0.025

ClinPred

0.0068

GERP RS

3.3

Varity_R

0.19

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over