1-248180688-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001004688.2(OR2M2):c.703T>C(p.Cys235Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,612,124 control chromosomes in the GnomAD database, including 326,238 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C235Y) has been classified as Benign.

Frequency

Genomes: 𝑓 0.62 ( 29369 hom., cov: 32)

Exomes 𝑓: 0.64 ( 296869 hom. )

Consequence

OR2M2
NM_001004688.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.27

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.7955297E-6).

BP6

Variant 1-248180688-T-C is Benign according to our data. Variant chr1-248180688-T-C is described in ClinVar as [Benign]. Clinvar id is 767775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2M2	NM_001004688.2 link	c.703T>C	p.Cys235Arg	missense_variant	Exon 2 of 2	ENST00000641836.1	NP_001004688.1	Q96R28A0A126GWI7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2M2	ENST00000641836.1 link	c.703T>C	p.Cys235Arg	missense_variant	Exon 2 of 2		NM_001004688.2	ENSP00000493201.1		Q96R28
OR2M2	ENST00000641211.1 link	c.703T>C	p.Cys235Arg	missense_variant	Exon 3 of 3			ENSP00000492974.1		Q96R28

Frequencies

GnomAD3 genomes

AF:

0.619

AC:

94122

AN:

151942

Hom.:

29337

Cov.:

show subpopulations

Gnomad AFR

AF:

0.596

Gnomad AMI

AF:

0.650

Gnomad AMR

AF:

0.621

Gnomad ASJ

AF:

0.557

Gnomad EAS

AF:

0.427

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.629

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.650

Gnomad OTH

AF:

0.639

GnomAD3 exomes

AF:

0.614

AC:

149832

AN:

244222

Hom.:

47209

AF XY:

0.619

AC XY:

81637

AN XY:

131968

show subpopulations

Gnomad AFR exome

AF:

0.601

Gnomad AMR exome

AF:

0.596

Gnomad ASJ exome

AF:

0.555

Gnomad EAS exome

AF:

0.432

Gnomad SAS exome

AF:

0.598

Gnomad FIN exome

AF:

0.635

Gnomad NFE exome

AF:

0.654

Gnomad OTH exome

AF:

0.633

GnomAD4 exome

AF:

0.636

AC:

928405

AN:

1460064

Hom.:

296869

Cov.:

AF XY:

0.635

AC XY:

461505

AN XY:

726396

show subpopulations

Gnomad4 AFR exome

AF:

0.603

Gnomad4 AMR exome

AF:

0.599

Gnomad4 ASJ exome

AF:

0.557

Gnomad4 EAS exome

AF:

0.438

Gnomad4 SAS exome

AF:

0.606

Gnomad4 FIN exome

AF:

0.637

Gnomad4 NFE exome

AF:

0.650

Gnomad4 OTH exome

AF:

0.632

GnomAD4 genome

AF:

0.619

AC:

94197

AN:

152060

Hom.:

29369

Cov.:

AF XY:

0.618

AC XY:

45904

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.596

Gnomad4 AMR

AF:

0.620

Gnomad4 ASJ

AF:

0.557

Gnomad4 EAS

AF:

0.427

Gnomad4 SAS

AF:

0.606

Gnomad4 FIN

AF:

0.629

Gnomad4 NFE

AF:

0.650

Gnomad4 OTH

AF:

0.636

Alfa

AF:

0.634

Hom.:

13166

Bravo

AF:

0.617

ESP6500AA

AF:

0.571

AC:

2517

ESP6500EA

AF:

0.627

AC:

5393

ExAC

AF:

0.611

AC:

74202

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 13, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.90

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.20

DANN

Benign

0.17

DEOGEN2

Benign

0.0045

T;T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00052

LIST_S2

Benign

0.0062

.;.;T

MetaRNN

Benign

0.0000038

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.5

N;N;N

PrimateAI

Benign

0.17

PROVEAN

Benign

5.1

.;.;N

REVEL

Benign

0.020

Sift

Benign

0.52

.;.;T

Sift4G

Benign

0.50

.;.;T

Polyphen

0.0

B;B;B

Vest4

0.0090

MPC

0.19

ClinPred

0.0042

GERP RS

1.1

Varity_R

0.074

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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