Variant 1-248038484-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001385855.1(OR2L2):c.217A>C(p.Ile73Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

OR2L2
NM_001385855.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.95

Variant links:

Genes affected

OR2L2 (HGNC:8266): (olfactory receptor family 2 subfamily L 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]

OR2L2 links:

OR2L13 (HGNC:):

OR2L13 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.068835944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR2L2	NM_001385855.1 linkuse as main transcript	c.217A>C	p.Ile73Leu	missense_variant	3/3	ENST00000641771.1
OR2L2	NM_001004686.3 linkuse as main transcript	c.217A>C	p.Ile73Leu	missense_variant	2/2
OR2L13	NM_001304535.3 linkuse as main transcript	c.-18-60874A>C		intron_variant
OR2L13	NM_175911.5 linkuse as main transcript	c.-143-60167A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Appris
OR2L2	ENST00000641771.1 linkuse as main transcript	c.217A>C	p.Ile73Leu	missense_variant	3/3	NM_001385855.1	P1
OR2L2	ENST00000366479.4 linkuse as main transcript	c.217A>C	p.Ile73Leu	missense_variant	1/1		P1
OR2L2	ENST00000642011.1 linkuse as main transcript	c.217A>C	p.Ile73Leu	missense_variant	2/2		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251386

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000792

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461574

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000244

Hom.:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2022

The c.217A>C (p.I73L) alteration is located in exon 1 (coding exon 1) of the OR2L2 gene. This alteration results from a A to C substitution at nucleotide position 217, causing the isoleucine (I) at amino acid position 73 to be replaced by a leucine (L). 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

0.16

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0064

T;T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.79

.;.;T

M_CAP

Benign

0.00040

MetaRNN

Benign

0.069

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.8

M;M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.6

.;.;N

REVEL

Benign

0.042

Sift

Uncertain

0.0080

.;.;D

Sift4G

Uncertain

0.017

.;.;D

Polyphen

0.31

B;B;B

Vest4

0.071

MutPred

0.32

Gain of catalytic residue at I73 (P = 0.0841);Gain of catalytic residue at I73 (P = 0.0841);Gain of catalytic residue at I73 (P = 0.0841);

MVP

0.076

MPC

0.016

ClinPred

0.073

GERP RS

-1.4

Varity_R

0.34

gMVP

0.17

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

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