11-6921612-C-G

Position:

• chr11-6921612-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001004684.1(OR2D3):​c.611C>G​(p.Ala204Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR2D3 NM_001004684.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39118236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2D3	NM_001004684.1	c.611C>G	p.Ala204Gly	missense_variant	1/1	ENST00000317834.5	NP_001004684.1
LOC107984019	XR_001748111.2	n.931+2886G>C		intron_variant
LOC107984019	XR_001748112.3	n.1466+2886G>C		intron_variant
LOC107984019	XR_007062575.1	n.980+2886G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2D3	ENST00000317834.5	c.611C>G	p.Ala204Gly	missense_variant	1/1	6	NM_001004684.1	ENSP00000320560.3
ENSG00000283415	ENST00000637205.2	n.605+2886G>C		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.611C>G (p.A204G) alteration is located in exon 1 (coding exon 1) of the OR2D3 gene. This alteration results from a C to G substitution at nucleotide position 611, causing the alanine (A) at amino acid position 204 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0072	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Pathogenic	3.4	M
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.21
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.013	D
Polyphen		0.76	P
Vest4		0.28
MutPred		0.72		Loss of stability (P = 0.0302);
MVP		0.64
MPC		0.12
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.51
gMVP		0.10

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: rs1848951260; hg19: chr11-6942843;