NM_001001824.2:c.807G>T

Variant names:

• chr1-248650078-C-A
• rs751281848
• NM_001001824.2:c.807G>T

Variant summary

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

The NM_001001824.2(OR2T27):​c.807G>T​(p.Glu269Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000317 in 1,573,434 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E269A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00035 (4 hom., cov: 26)
  • Exomes 𝑓: 0.00031 (30 hom.)
• Consequence: OR2T27 NM_001001824.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.66
• Publications: 3 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=0.0044091344).
• 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.807G>T	p.Glu269Asp	missense	Exon 2 of 2	NP_001001824.1	Q8NH04
	OR2T27	NM_001386060.1		c.807G>T	p.Glu269Asp	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.807G>T	p.Glu269Asp	missense	Exon 2 of 2	ENSP00000493412.1	Q8NH04
	OR2T27	ENST00000641652.1		c.807G>T	p.Glu269Asp	missense	Exon 3 of 3	ENSP00000493434.1	Q8NH04

Frequencies

GnomAD3 genomes AF: 0.000353 AC: 51 AN: 144376 Hom.: 4 Cov.: 26

Gnomad AFR AF: 0.0000260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000479

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: 0.00100

GnomAD2 exomes AF: 0.000359 AC: 88 AN: 245428 AF XY: 0.000331

Gnomad AFR exome AF: 0.0000644

Gnomad AMR exome AF: 0.000237

Gnomad ASJ exome AF: 0.00512

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000207

Gnomad OTH exome AF: 0.000831

GnomAD4 exome AF: 0.000313 AC: 447 AN: 1429058 Hom.: 30 Cov.: 33 AF XY: 0.000283 AC XY: 201 AN XY: 711450

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

African (AFR) AF: 0.0000312 AC: 1 AN: 32042

American (AMR) AF: 0.000525 AC: 23 AN: 43824

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 179 AN: 25854

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38564

South Asian (SAS) AF: 0.0000356 AC: 3 AN: 84264

European-Finnish (FIN) AF: 0.0000388 AC: 2 AN: 51552

Middle Eastern (MID) AF: 0.000878 AC: 5 AN: 5696

European-Non Finnish (NFE) AF: 0.000176 AC: 192 AN: 1088036

Other (OTH) AF: 0.000692 AC: 41 AN: 59226

⚠️ 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: 0.000353 AC: 51 AN: 144376 Hom.: 4 Cov.: 26 AF XY: 0.000485 AC XY: 34 AN XY: 70162

African (AFR) AF: 0.0000260 AC: 1 AN: 38454

American (AMR) AF: 0.000479 AC: 7 AN: 14626

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4862

South Asian (SAS) AF: 0.00 AC: 0 AN: 4426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9548

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

European-Non Finnish (NFE) AF: 0.000167 AC: 11 AN: 65860

Other (OTH) AF: 0.00100 AC: 2 AN: 1998

Alfa AF: 0.00106 Hom.: 3

ExAC AF: 0.000450 AC: 54

EpiCase AF: 0.00

EpiControl AF: 0.000301

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	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.90
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.00099	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.7
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.013
Sift	Benign	0.14	T
Sift4G	Benign	0.40	T
Polyphen		0.044	B
Vest4		0.070
MutPred		0.29		Loss of ubiquitination at K272 (P = 0.1055)
MVP		0.28
MPC		0.45
ClinPred		0.017	T
GERP RS		0.29
Varity_R		0.11
gMVP		0.067
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs751281848; hg19: chr1-248813379; COSMIC: COSV61282705; COSMIC: COSV61282705;