Variant 1-247966000-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001004491.2(OR2AK2):c.624A>G(p.Leu208=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,612,744 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0068 ( 15 hom., cov: 33)

Exomes 𝑓: 0.00081 ( 12 hom. )

Consequence

OR2AK2
NM_001004491.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.28

Variant links:

Genes affected

OR2AK2 (HGNC:19569): (olfactory receptor family 2 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]

OR2AK2 links:

OR2L13 (HGNC:):

OR2L13 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 1-247966000-A-G is Benign according to our data. Variant chr1-247966000-A-G is described in ClinVar as [Benign]. Clinvar id is 719380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00682 (1038/152260) while in subpopulation AFR AF= 0.023 (955/41534). AF 95% confidence interval is 0.0218. There are 15 homozygotes in gnomad4. There are 507 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
OR2AK2	NM_001004491.2 linkuse as main transcript	c.624A>G	p.Leu208=	synonymous_variant	1/1	ENST00000366480.5	NP_001004491.2
OR2L13	NM_001304535.3 linkuse as main transcript	c.-19+28616A>G		intron_variant			NP_001291464.1
OR2L13	NM_175911.5 linkuse as main transcript	c.-144+28616A>G		intron_variant			NP_787107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2AK2	ENST00000366480.5 linkuse as main transcript	c.624A>G	p.Leu208=	synonymous_variant	1/1		NM_001004491.2	ENSP00000355436	P1

Frequencies

GnomAD3 genomes

AF:

0.00673

AC:

1024

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00189

AC:

471

AN:

249626

Hom.:

AF XY:

0.00148

AC XY:

199

AN XY:

134822

show subpopulations

Gnomad AFR exome

AF:

0.0228

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.00344

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000660

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000186

Gnomad OTH exome

AF:

0.000988

GnomAD4 exome

AF:

0.000811

AC:

1184

AN:

1460484

Hom.:

Cov.:

AF XY:

0.000761

AC XY:

553

AN XY:

726476

show subpopulations

Gnomad4 AFR exome

AF:

0.0233

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.00273

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000465

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000119

Gnomad4 OTH exome

AF:

0.00232

GnomAD4 genome

AF:

0.00682

AC:

1038

AN:

152260

Hom.:

Cov.:

AF XY:

0.00681

AC XY:

507

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0230

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00360

Hom.:

Bravo

AF:

0.00783

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.91

DANN

Benign

0.67

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