11-6891596-A-G

Variant names:

• chr11-6891596-A-G
• rs117454717
• NM_003700.1:c.905T>C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003700.1(OR2D2):​c.905T>C​(p.Val302Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,612,832 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (2 hom.)
• Consequence: OR2D2 NM_003700.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.200

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016853273).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2D2	NM_003700.1	c.905T>C	p.Val302Ala	missense_variant	Exon 1 of 1	ENST00000299459.3	NP_003691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2D2	ENST00000299459.3	c.905T>C	p.Val302Ala	missense_variant	Exon 1 of 1	6	NM_003700.1	ENSP00000299459.2
ENSG00000283415	ENST00000637205.2	n.605+32902T>C		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.000460 AC: 70 AN: 152116 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000487 AC: 122 AN: 250424 Hom.: 0 AF XY: 0.000510 AC XY: 69 AN XY: 135328

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.000790

Gnomad NFE exome AF: 0.000866

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.00106 AC: 1553 AN: 1460598 Hom.: 2 Cov.: 30 AF XY: 0.000986 AC XY: 716 AN XY: 726488

Gnomad4 AFR exome AF: 0.000180

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.000956

Gnomad4 NFE exome AF: 0.00131

Gnomad4 OTH exome AF: 0.000597

GnomAD4 genome AF: 0.000460 AC: 70 AN: 152234 Hom.: 0 Cov.: 31 AF XY: 0.000363 AC XY: 27 AN XY: 74440

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000660

Gnomad4 NFE AF: 0.000838

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000700 Hom.: 0

Bravo AF: 0.000438

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000931 AC: 8

ExAC AF: 0.000412 AC: 50

EpiCase AF: 0.000655

EpiControl AF: 0.000889

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.905T>C (p.V302A) alteration is located in exon 1 (coding exon 1) of the OR2D2 gene. This alteration results from a T to C substitution at nucleotide position 905, causing the valine (V) at amino acid position 302 to be replaced by an alanine (A). 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	0.076
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.7
DANN	Benign	0.77
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Benign	0.31	T
Sift4G	Benign	0.14	T
Polyphen		0.0010	B
Vest4		0.15
MVP		0.44
MPC		0.015
ClinPred		0.016	T
GERP RS		5.1
Varity_R		0.14
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs117454717; hg19: chr11-6912827;