Variant 11-56989820-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005323.1(OR5AK2):c.907G>T(p.Val303Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000346 in 1,589,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

OR5AK2
NM_001005323.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.19

Variant links:

Genes affected

OR5AK2 (HGNC:15251): (olfactory receptor family 5 subfamily AK 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]

OR5AK2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.022931188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5AK2	NM_001005323.1 link	c.907G>T	p.Val303Leu	missense_variant	1/1	ENST00000326855.3	NP_001005323.1	Q8NH90A0A126GW20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5AK2	ENST00000326855.3 link	c.907G>T	p.Val303Leu	missense_variant	1/1	6	NM_001005323.1	ENSP00000322784.2		Q8NH90

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000512

AC:

AN:

234382

Hom.:

AF XY:

0.0000468

AC XY:

AN XY:

128090

show subpopulations

Gnomad AFR exome

AF:

0.000207

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000114

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000650

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000306

AC:

AN:

1437164

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

715528

show subpopulations

Gnomad4 AFR exome

AF:

0.0000929

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000346

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.0000746

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.44

DANN

Benign

0.43

DEOGEN2

Benign

0.00067

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.041

M_CAP

Benign

0.0037

MetaRNN

Benign

0.023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.85

REVEL

Benign

0.029

Sift

Benign

0.24

Sift4G

Benign

0.45

Polyphen

0.0010

Vest4

0.059

MutPred

0.46

Loss of methylation at K302 (P = 0.0453);

MVP

0.061

ClinPred

0.017

GERP RS

-2.9

Varity_R

0.10

gMVP

0.055

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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