NM_001001915.1:c.500T>A

Variant names:

• chr1-247588859-T-A
• rs10925085
• NM_001001915.1:c.500T>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001001915.1(OR2G2):​c.500T>A​(p.Leu167Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. L167P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OR2G2 NM_001001915.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.859

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]

ENSG00000236817 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28416604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2G2	NM_001001915.1	c.500T>A	p.Leu167Gln	missense_variant	Exon 1 of 1	ENST00000320065.1	NP_001001915.1
LOC102724446	NR_188589.1	n.226-22908A>T		intron_variant	Intron 2 of 2
LOC102724446	NR_188590.1	n.438-22908A>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2G2	ENST00000320065.1	c.500T>A	p.Leu167Gln	missense_variant	Exon 1 of 1	6	NM_001001915.1	ENSP00000326349.1
ENSG00000236817	ENST00000435333.5	n.226-22908A>T		intron_variant	Intron 2 of 2	3
ENSG00000236817	ENST00000446347.1	n.438-22908A>T		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0074	T
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.094	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.049
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.34		Loss of stability (P = 0.1681);
MVP		0.59
MPC		0.36
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.50
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs10925085; hg19: chr1-247752161;