Variant 7-144318179-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005287.2(OR2A1):c.55G>A(p.Gly19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 17)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR2A1
NM_001005287.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.640

Variant links:

Genes affected

OR2A1 (HGNC:8229): (olfactory receptor family 2 subfamily A member 1) 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]

OR2A1 links:

OR2A1-AS1 (HGNC:49168): (OR2A1 antisense RNA 1)

OR2A1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.056833357).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR2A1	NM_001005287.2 linkuse as main transcript	c.55G>A	p.Gly19Ser	missense_variant	2/2	ENST00000641044.2
OR2A1-AS1	NR_126023.1 linkuse as main transcript	n.494-6475C>T		intron_variant, non_coding_transcript_variant
OR2A1	XM_047420323.1 linkuse as main transcript	c.55G>A	p.Gly19Ser	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2A1	ENST00000641044.2 linkuse as main transcript	c.55G>A	p.Gly19Ser	missense_variant	2/2		NM_001005287.2	P1
OR2A1-AS1	ENST00000496968.5 linkuse as main transcript	n.296-6240C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

131310

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000589

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

633846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

337364

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000152

AC:

AN:

131310

Hom.:

Cov.:

AF XY:

0.0000158

AC XY:

AN XY:

63346

show subpopulations

Gnomad4 AFR

AF:

0.0000589

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:

0.00

Gnomad4 OTH

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 16, 2021

The c.55G>A (p.G19S) alteration is located in exon 1 (coding exon 1) of the OR2A1 gene. This alteration results from a G to A substitution at nucleotide position 55, causing the glycine (G) at amino acid position 19 to be replaced by a serine (S). 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

0.093

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.3

DANN

Benign

0.41

DEOGEN2

Benign

0.0019

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.015

.;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.057

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

-1.1

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.19

PROVEAN

Benign

0.37

.;N

REVEL

Benign

0.016

Sift

Benign

0.55

.;T

Sift4G

Benign

0.66

.;T

Vest4

0.15

MutPred

0.34

Loss of catalytic residue at G19 (P = 0.1642);Loss of catalytic residue at G19 (P = 0.1642);

MVP

0.18

ClinPred

0.041

GERP RS

0.91

Varity_R

0.026

gMVP

0.11

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