Variant 11-4449527-T-G details in Genebe, Genetics Data Aggregator

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

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]

OR52K2 links:

(HGNC:):

links:

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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
OR52K2	NM_001005172.2 linkuse as main transcript	c.188T>G	p.Leu63Arg	missense_variant	1/1	ENST00000325719.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR52K2	ENST00000325719.4 linkuse as main transcript	c.188T>G	p.Leu63Arg	missense_variant	1/1		NM_001005172.2	P1
	ENST00000690302.1 linkuse as main transcript	n.379+55362T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250962

Hom.:

AF XY:

0.00000737

AC XY:

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.:

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The 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

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

Eigen

Benign

0.11

Eigen_PC

Benign

0.048

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.84

M_CAP

Benign

0.0095

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

0.58

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.19

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0040

Polyphen

0.55

Vest4

0.64

MutPred

0.70

Gain of methylation at L63 (P = 0.0179);

MVP

0.44

MPC

0.0042

ClinPred

0.92

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.

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