NM_001001824.2:c.818C>G

Variant names:

• chr1-248650067-G-C
• rs750254363
• NM_001001824.2:c.818C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001001824.2(OR2T27):​c.818C>G​(p.Ala273Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000321 in 1,572,536 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00036 (4 hom., cov: 26)
  • Exomes 𝑓: 0.00032 (32 hom.)
• Consequence: OR2T27 NM_001001824.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.315
• Publications: 1 publications found

Genes affected

OR2T27 (HGNC:31252): (olfactory receptor family 2 subfamily T member 27) 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011996597).
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001824.2. 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
	OR2T27	NM_001001824.2	MANE Select	c.818C>G	p.Ala273Gly	missense	Exon 2 of 2	NP_001001824.1	Q8NH04
	OR2T27	NM_001386060.1		c.818C>G	p.Ala273Gly	missense	Exon 3 of 3	NP_001372989.1	Q8NH04

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T27	ENST00000460972.4	TSL:6 MANE Select	c.818C>G	p.Ala273Gly	missense	Exon 2 of 2	ENSP00000493412.1	Q8NH04
	OR2T27	ENST00000641652.1		c.818C>G	p.Ala273Gly	missense	Exon 3 of 3	ENSP00000493434.1	Q8NH04

Frequencies

GnomAD3 genomes AF: 0.000360 AC: 52 AN: 144536 Hom.: 4 Cov.: 26

Gnomad AFR AF: 0.0000520

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000478

Gnomad ASJ AF: 0.00881

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000167

Gnomad OTH AF: 0.000998

GnomAD2 exomes AF: 0.000346 AC: 85 AN: 245642 AF XY: 0.000331

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000236

Gnomad ASJ exome AF: 0.00502

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000197

Gnomad OTH exome AF: 0.000831

GnomAD4 exome AF: 0.000317 AC: 452 AN: 1428000 Hom.: 32 Cov.: 33 AF XY: 0.000287 AC XY: 204 AN XY: 710966

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000315 AC: 1 AN: 31760

American (AMR) AF: 0.000525 AC: 23 AN: 43820

Ashkenazi Jewish (ASJ) AF: 0.00711 AC: 184 AN: 25862

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38552

South Asian (SAS) AF: 0.0000356 AC: 3 AN: 84260

European-Finnish (FIN) AF: 0.0000388 AC: 2 AN: 51560

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5694

European-Non Finnish (NFE) AF: 0.000175 AC: 190 AN: 1087320

Other (OTH) AF: 0.000710 AC: 42 AN: 59172

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000360 AC: 52 AN: 144536 Hom.: 4 Cov.: 26 AF XY: 0.000498 AC XY: 35 AN XY: 70226

African (AFR) AF: 0.0000520 AC: 2 AN: 38440

American (AMR) AF: 0.000478 AC: 7 AN: 14638

Ashkenazi Jewish (ASJ) AF: 0.00881 AC: 30 AN: 3406

East Asian (EAS) AF: 0.00 AC: 0 AN: 4864

South Asian (SAS) AF: 0.00 AC: 0 AN: 4440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000167 AC: 11 AN: 65958

Other (OTH) AF: 0.000998 AC: 2 AN: 2004

Alfa AF: 0.00120 Hom.: 3

ExAC AF: 0.000450 AC: 54

EpiCase AF: 0.00

EpiControl AF: 0.000300

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.92	T
PhyloP100		0.32
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.057
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.038	D
Polyphen		0.85	P
Vest4		0.29
MutPred		0.52		Gain of ubiquitination at K272 (P = 0.0913)
MVP		0.33
MPC		0.92
ClinPred		0.10	T
GERP RS		-0.78
Varity_R		0.51
gMVP		0.029
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs750254363; hg19: chr1-248813368;