11-4449796-C-G

Variant names:

• chr11-4449796-C-G
• rs143862015
• NM_001005172.2:c.457C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001005172.2(OR52K2):​c.457C>G​(p.Arg153Gly) 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 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R153W) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OR52K2 NM_001005172.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 1 publications found

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]

ENSG00000291144 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005172.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52K2	NM_001005172.2	MANE Select	c.457C>G	p.Arg153Gly	missense	Exon 1 of 1	NP_001005172.2	Q8NGK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52K2	ENST00000325719.4	TSL:6 MANE Select	c.457C>G	p.Arg153Gly	missense	Exon 1 of 1	ENSP00000318956.4	Q8NGK3
	ENSG00000291144	ENST00000641797.5		n.387-19571C>G		intron	N/A
	ENSG00000291144	ENST00000685350.2		n.392-19571C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251172 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0031	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		-1.8
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Benign	0.092
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.83	P
Vest4		0.47
MutPred		0.63		Loss of methylation at R153 (P = 0.0104)
MVP		0.16
MPC		0.0034
ClinPred		0.89	D
GERP RS		2.1
Varity_R		0.68
gMVP		0.35
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs143862015; hg19: chr11-4471026;