Variant chr1-248038499-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001385855.1(OR2L2):c.232C>A(p.Pro78Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR2L2	NM_001385855.1 linkuse as main transcript	c.232C>A	p.Pro78Thr	missense_variant	3/3	ENST00000641771.1
OR2L2	NM_001004686.3 linkuse as main transcript	c.232C>A	p.Pro78Thr	missense_variant	2/2
OR2L13	NM_001304535.3 linkuse as main transcript	c.-18-60859C>A		intron_variant
OR2L13	NM_175911.5 linkuse as main transcript	c.-143-60152C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Appris
OR2L2	ENST00000641771.1 linkuse as main transcript	c.232C>A	p.Pro78Thr	missense_variant	3/3	NM_001385855.1	P1
OR2L2	ENST00000366479.4 linkuse as main transcript	c.232C>A	p.Pro78Thr	missense_variant	1/1		P1
OR2L2	ENST00000642011.1 linkuse as main transcript	c.232C>A	p.Pro78Thr	missense_variant	2/2		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

May 02, 2024

The c.232C>A (p.P78T) alteration is located in exon 1 (coding exon 1) of the OR2L2 gene. This alteration results from a C to A substitution at nucleotide position 232, causing the proline (P) at amino acid position 78 to be replaced by a threonine (T). 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

Uncertain

0.45

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

T;T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.086

LIST_S2

Uncertain

0.90

.;.;D

M_CAP

Benign

0.00075

MetaRNN

Uncertain

0.43

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.9

H;H;H

MutationTaster

Benign

0.78

N;N

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-7.5

.;.;D

REVEL

Benign

0.089

Sift

Pathogenic

0.0

.;.;D

Sift4G

Uncertain

0.0080

.;.;D

Polyphen

0.99

D;D;D

Vest4

0.49

MutPred

0.58

Loss of glycosylation at T75 (P = 0.0537);Loss of glycosylation at T75 (P = 0.0537);Loss of glycosylation at T75 (P = 0.0537);

MVP

0.27

MPC

0.088

ClinPred

0.69

GERP RS

0.96

Varity_R

0.59

gMVP

0.30

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over