Variant 1-248180245-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001004688.2(OR2M2):c.260C>G(p.Ser87Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,614,154 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.011 ( 23 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 38 hom. )

Consequence

OR2M2
NM_001004688.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.892

Variant links:

Genes affected

OR2M2 (HGNC:8268): (olfactory receptor family 2 subfamily M 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]

OR2M2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066441298).

BP6

Variant 1-248180245-C-G is Benign according to our data. Variant chr1-248180245-C-G is described in ClinVar as [Benign]. Clinvar id is 783020.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1682/152288) while in subpopulation AFR AF= 0.0385 (1599/41538). AF 95% confidence interval is 0.0369. There are 23 homozygotes in gnomad4. There are 849 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2M2	NM_001004688.2 linkuse as main transcript	c.260C>G	p.Ser87Cys	missense_variant	2/2	ENST00000641836.1	NP_001004688.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2M2	ENST00000641836.1 linkuse as main transcript	c.260C>G	p.Ser87Cys	missense_variant	2/2		NM_001004688.2	ENSP00000493201	P1
OR2M2	ENST00000641211.1 linkuse as main transcript	c.260C>G	p.Ser87Cys	missense_variant	3/3			ENSP00000492974	P1

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1656

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0380

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00438

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00288

AC:

725

AN:

251446

Hom.:

AF XY:

0.00201

AC XY:

273

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0378

Gnomad AMR exome

AF:

0.00283

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00119

AC:

1744

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

746

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0406

Gnomad4 AMR exome

AF:

0.00291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.00341

GnomAD4 genome

AF:

0.0110

AC:

1682

AN:

152288

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

849

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0385

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00319

Hom.:

Bravo

AF:

0.0120

ESP6500AA

AF:

0.0377

AC:

166

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00347

AC:

421

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 07, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.014

T;T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.29

.;.;T

MetaRNN

Benign

0.0066

T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Pathogenic

3.0

M;M;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-3.3

.;.;D

REVEL

Benign

0.23

Sift

Uncertain

0.020

.;.;D

Sift4G

Benign

0.072

.;.;T

Polyphen

1.0

D;D;D

Vest4

0.16

MVP

0.76

MPC

0.53

ClinPred

0.068

GERP RS

-2.3

Varity_R

0.15

gMVP

0.039

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