Variant chr1-248650212-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001001824.2(OR2T27):c.673G>C(p.Val225Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000735 in 135,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000074 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0000066 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

OR2T27
NM_001001824.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.319

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14722878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T27	NM_001001824.2 linkuse as main transcript	c.673G>C	p.Val225Leu	missense_variant	2/2	ENST00000460972.4
OR2T27	NM_001386060.1 linkuse as main transcript	c.673G>C	p.Val225Leu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T27	ENST00000460972.4 linkuse as main transcript	c.673G>C	p.Val225Leu	missense_variant	2/2		NM_001001824.2	P1
OR2T27	ENST00000641652.1 linkuse as main transcript	c.673G>C	p.Val225Leu	missense_variant	3/3			P1

Frequencies

GnomAD3 genomes

AF:

0.00000736

AC:

AN:

135856

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000224

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000425

AC:

AN:

211648

Hom.:

AF XY:

0.0000530

AC XY:

AN XY:

113308

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000576

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000662

AC:

AN:

1360452

Hom.:

Cov.:

AF XY:

0.00000738

AC XY:

AN XY:

677570

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000240

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000735

AC:

AN:

135976

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

65526

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000225

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000594

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

Jan 17, 2024

The c.673G>C (p.V225L) alteration is located in exon 1 (coding exon 1) of the OR2T27 gene. This alteration results from a G to C substitution at nucleotide position 673, causing the valine (V) at amino acid position 225 to be replaced by a leucine (L). 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

0.23

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

T;T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.067

LIST_S2

Uncertain

0.89

.;.;D

M_CAP

Benign

0.0012

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

-2.3

.;.;N

REVEL

Benign

0.11

Sift

Uncertain

0.0010

.;.;D

Sift4G

Uncertain

0.0020

.;.;D

Polyphen

0.97

D;D;D

Vest4

0.24

MutPred

0.61

Gain of catalytic residue at V225 (P = 0.0056);Gain of catalytic residue at V225 (P = 0.0056);Gain of catalytic residue at V225 (P = 0.0056);

MVP

0.49

MPC

1.4

ClinPred

0.26

GERP RS

2.5

Varity_R

0.65

gMVP

0.082

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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