11-4449527-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001005172.2(OR52K2):​c.188T>G​(p.Leu63Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

OR52K2
NM_001005172.2 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.421
Variant links:
Genes affected
OR52K2 (HGNC:15223): (olfactory receptor family 52 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR52K2NM_001005172.2 linkuse as main transcriptc.188T>G p.Leu63Arg missense_variant 1/1 ENST00000325719.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR52K2ENST00000325719.4 linkuse as main transcriptc.188T>G p.Leu63Arg missense_variant 1/1 NM_001005172.2 P1
ENST00000690302.1 linkuse as main transcriptn.379+55362T>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250962
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135606
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 01, 2024The c.188T>G (p.L63R) alteration is located in exon 1 (coding exon 1) of the OR52K2 gene. This alteration results from a T to G substitution at nucleotide position 188, causing the leucine (L) at amino acid position 63 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.010
T
Eigen
Benign
0.11
Eigen_PC
Benign
0.048
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.0095
T
MetaRNN
Uncertain
0.70
D
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.8
M
MutationTaster
Benign
0.58
D
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-3.7
D
REVEL
Benign
0.19
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.0040
D
Polyphen
0.55
P
Vest4
0.64
MutPred
0.70
Gain of methylation at L63 (P = 0.0179);
MVP
0.44
MPC
0.0042
ClinPred
0.92
D
GERP RS
4.4
Varity_R
0.77
gMVP
0.45

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.

Other links and lift over

dbSNP: rs1476649790; hg19: chr11-4470757; API