Genetic Variant NM_001001915.1:c.500T>C (chr1-247588859-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001001915.1(OR2G2):c.500T>C(p.Leu167Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,613,912 control chromosomes in the GnomAD database, including 125,326 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.31 ( 8947 hom., cov: 33)

Exomes 𝑓: 0.39 ( 116379 hom. )

Consequence

OR2G2
NM_001001915.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.859

Variant links:

Genes affected

OR2G2 (HGNC:15007): (olfactory receptor family 2 subfamily G 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]

OR2G2 links:

ENSG00000236817 (HGNC:):

ENSG00000236817 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.9362569E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2G2	NM_001001915.1 link	c.500T>C	p.Leu167Pro	missense_variant	Exon 1 of 1	ENST00000320065.1	NP_001001915.1	Q8NGZ5
LOC102724446	NR_188589.1 link	n.226-22908A>G		intron_variant	Intron 2 of 2
LOC102724446	NR_188590.1 link	n.438-22908A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR2G2	ENST00000320065.1 link	c.500T>C	p.Leu167Pro	missense_variant	Exon 1 of 1	6	NM_001001915.1	ENSP00000326349.1	Q8NGZ5
ENSG00000236817	ENST00000435333.5 link	n.226-22908A>G		intron_variant	Intron 2 of 2	3
ENSG00000236817	ENST00000446347.1 link	n.438-22908A>G		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47849

AN:

152024

Hom.:

8950

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.410

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.516

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.357

GnomAD3 exomes

AF:

0.370

AC:

92829

AN:

250958

Hom.:

18283

AF XY:

0.371

AC XY:

50261

AN XY:

135610

show subpopulations

Gnomad AFR exome

AF:

0.0935

Gnomad AMR exome

AF:

0.374

Gnomad ASJ exome

AF:

0.442

Gnomad EAS exome

AF:

0.527

Gnomad SAS exome

AF:

0.282

Gnomad FIN exome

AF:

0.372

Gnomad NFE exome

AF:

0.399

Gnomad OTH exome

AF:

0.393

GnomAD4 exome

AF:

0.394

AC:

575352

AN:

1461770

Hom.:

116379

Cov.:

AF XY:

0.390

AC XY:

283850

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0941

Gnomad4 AMR exome

AF:

0.374

Gnomad4 ASJ exome

AF:

0.440

Gnomad4 EAS exome

AF:

0.549

Gnomad4 SAS exome

AF:

0.279

Gnomad4 FIN exome

AF:

0.376

Gnomad4 NFE exome

AF:

0.407

Gnomad4 OTH exome

AF:

0.396

GnomAD4 genome

AF:

0.314

AC:

47847

AN:

152142

Hom.:

8947

Cov.:

AF XY:

0.313

AC XY:

23264

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.368

Gnomad4 ASJ

AF:

0.444

Gnomad4 EAS

AF:

0.516

Gnomad4 SAS

AF:

0.293

Gnomad4 FIN

AF:

0.373

Gnomad4 NFE

AF:

0.400

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.384

Hom.:

19778

Bravo

AF:

0.311

TwinsUK

AF:

0.416

AC:

1542

ALSPAC

AF:

0.409

AC:

1576

ESP6500AA

AF:

0.106

AC:

465

ESP6500EA

AF:

0.403

AC:

3464

ExAC

AF:

0.362

AC:

43966

Asia WGS

AF:

0.404

AC:

1403

AN:

3478

EpiCase

AF:

0.413

EpiControl

AF:

0.414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0080

Eigen

Uncertain

0.32

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.33

MetaRNN

Benign

0.00019

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.057

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.17

MPC

0.43

ClinPred

0.049

GERP RS

4.3

Varity_R

0.76

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over