dbSNP rs138993605: OR2K2:p.Arg54Pro (chr9-111328273-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_205859.2(OR2K2):c.161G>C(p.Arg54Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R54H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OR2K2
NM_205859.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.67

Variant links:

Genes affected

OR2K2 (HGNC:8264): (olfactory receptor family 2 subfamily K 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]

OR2K2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25145873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2K2	NM_205859.2 link	c.161G>C	p.Arg54Pro	missense_variant	Exon 2 of 2	ENST00000302681.3	NP_995581.1	Q8NGT1A0A0C4DFP3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2K2	ENST00000302681.3 link	c.161G>C	p.Arg54Pro	missense_variant	Exon 2 of 2	6	NM_205859.2	ENSP00000305055.1		Q8NGT1
OR2K2	ENST00000374428.1 link	c.248G>C	p.Arg83Pro	missense_variant	Exon 1 of 1	6		ENSP00000363550.1		A0A494BX18

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111990

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.6

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0094

T;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.20

T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.

PhyloP100

-2.7

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.15

Sift

Benign

0.043

D;T

Sift4G

Uncertain

0.030

D;D

Polyphen

0.99

D;.

Vest4

0.53

MutPred

0.48

Gain of methylation at K85 (P = 0.0373);.;

MVP

0.030

MPC

0.17

ClinPred

0.64

GERP RS

-4.3

PromoterAI

0.014

Neutral

(source)

Varity_R

0.40

gMVP

0.52

Mutation Taster

=95/5

polymorphism

(source)

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

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rs138993605

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

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