Variant 1-248650176-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001001824.2(OR2T27):c.709G>T(p.Ala237Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,564,902 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000019 ( 3 hom. )

Consequence

OR2T27
NM_001001824.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29

Variant links:

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]

OR2T27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.41777077).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2T27	NM_001001824.2 linkuse as main transcript	c.709G>T	p.Ala237Ser	missense_variant	2/2	ENST00000460972.4	NP_001001824.1	Q8NH04
OR2T27	NM_001386060.1 linkuse as main transcript	c.709G>T	p.Ala237Ser	missense_variant	3/3		NP_001372989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2T27	ENST00000460972.4 linkuse as main transcript	c.709G>T	p.Ala237Ser	missense_variant	2/2	6	NM_001001824.2	ENSP00000493412.1		Q8NH04
OR2T27	ENST00000641652.1 linkuse as main transcript	c.709G>T	p.Ala237Ser	missense_variant	3/3			ENSP00000493434.1		Q8NH04

Frequencies

GnomAD3 genomes

AF:

0.0000353

AC:

AN:

141776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000705

Gnomad ASJ

AF:

0.000896

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000514

GnomAD3 exomes

AF:

0.0000418

AC:

AN:

239238

Hom.:

AF XY:

0.0000309

AC XY:

AN XY:

129246

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000606

Gnomad EAS exome

AF:

0.000116

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000926

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000190

AC:

AN:

1423012

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

708102

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000232

Gnomad4 ASJ exome

AF:

0.000388

Gnomad4 EAS exome

AF:

0.0000782

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000831

Gnomad4 OTH exome

AF:

0.0000677

GnomAD4 genome

AF:

0.0000352

AC:

AN:

141890

Hom.:

Cov.:

AF XY:

0.0000726

AC XY:

AN XY:

68834

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000704

Gnomad4 ASJ

AF:

0.000896

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000509

Alfa

AF:

0.0000435

Hom.:

ExAC

AF:

0.0000336

AC:

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

Aug 03, 2022

The c.709G>T (p.A237S) alteration is located in exon 1 (coding exon 1) of the OR2T27 gene. This alteration results from a G to T substitution at nucleotide position 709, causing the alanine (A) at amino acid position 237 to be replaced by a serine (S). 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

0.17

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0086

T;T;T

Eigen

Uncertain

0.24

Eigen_PC

Benign

-0.0017

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.83

.;.;T

M_CAP

Benign

0.00089

MetaRNN

Benign

0.42

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-2.8

.;.;D

REVEL

Benign

0.12

Sift

Uncertain

0.0040

.;.;D

Sift4G

Uncertain

0.043

.;.;D

Polyphen

1.0

D;D;D

Vest4

0.43

MutPred

0.59

Gain of disorder (P = 0.0288);Gain of disorder (P = 0.0288);Gain of disorder (P = 0.0288);

MVP

0.62

MPC

1.3

ClinPred

0.52

GERP RS

2.5

Varity_R

0.33

gMVP

0.043

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