1-248099551-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001395936.1(OR2L13):c.176A>G(p.Tyr59Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000235 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

OR2L13
NM_001395936.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61

Variant links:

Genes affected

OR2L13 (HGNC:19578): (olfactory receptor family 2 subfamily L member 13) 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]

OR2L13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.8

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2L13	NM_001395936.1 link	c.176A>G	p.Tyr59Cys	missense_variant	Exon 3 of 3	ENST00000358120.4	NP_001382865.1
OR2L13	NM_001304535.3 link	c.176A>G	p.Tyr59Cys	missense_variant	Exon 2 of 2		NP_001291464.1	Q8N349A0A126GW96
OR2L13	NM_175911.5 link	c.176A>G	p.Tyr59Cys	missense_variant	Exon 3 of 3		NP_787107.1	Q8N349A0A126GW96
OR2L13	XM_011544169.3 link	c.176A>G	p.Tyr59Cys	missense_variant	Exon 3 of 3		XP_011542471.1	Q8N349A0A126GW96

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR2L13	ENST00000358120.4 link	c.176A>G	p.Tyr59Cys	missense_variant	Exon 3 of 3	6	NM_001395936.1	ENSP00000350836.2	Q8N349
OR2L13	ENST00000641714.1 link	c.176A>G	p.Tyr59Cys	missense_variant	Exon 3 of 3			ENSP00000493075.1	Q8N349
OR2L13	ENST00000641893.1 link	c.176A>G	p.Tyr59Cys	missense_variant	Exon 2 of 2			ENSP00000492949.1	Q8N349

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251470

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135906

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:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727242

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:

0.0000187

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152002

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.176A>G (p.Y59C) alteration is located in exon 3 (coding exon 1) of the OR2L13 gene. This alteration results from a A to G substitution at nucleotide position 176, causing the tyrosine (Y) at amino acid position 59 to be replaced by a cysteine (C). 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

0.27

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.83

.;.;T

M_CAP

Benign

0.0016

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Benign

-0.56

MutationAssessor

Pathogenic

3.6

H;H;H

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-8.3

D;.;.

REVEL

Benign

0.15

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;.;.

Polyphen

1.0

D;D;D

Vest4

0.38

MutPred

0.63

Loss of stability (P = 0.3212);Loss of stability (P = 0.3212);Loss of stability (P = 0.3212);

MVP

0.62

ClinPred

1.0

GERP RS

2.9

Varity_R

0.82

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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