Variant chr7-144075058-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001386096.1(OR2A25):c.839T>C(p.Phe280Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OR2A25
NM_001386096.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39

Variant links:

Genes affected

OR2A25 (HGNC:19562): (olfactory receptor family 2 subfamily A member 25) 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]

OR2A25 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2A25	NM_001386096.1 linkuse as main transcript	c.839T>C	p.Phe280Ser	missense_variant	2/2	ENST00000641663.1
OR2A25	NM_001004488.2 linkuse as main transcript	c.839T>C	p.Phe280Ser	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Appris
OR2A25	ENST00000641663.1 linkuse as main transcript	c.839T>C	p.Phe280Ser	missense_variant	2/2	NM_001386096.1	P1
OR2A25	ENST00000408898.2 linkuse as main transcript	c.839T>C	p.Phe280Ser	missense_variant	1/1		P1
OR2A25	ENST00000641441.1 linkuse as main transcript	c.839T>C	p.Phe280Ser	missense_variant	2/2		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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

Cov.:

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

Mar 01, 2023

The c.839T>C (p.F280S) alteration is located in exon 1 (coding exon 1) of the OR2A25 gene. This alteration results from a T to C substitution at nucleotide position 839, causing the phenylalanine (F) at amino acid position 280 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

0.21

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;T;T

Eigen

Uncertain

0.32

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.36

LIST_S2

Uncertain

0.95

.;.;D

M_CAP

Benign

0.0066

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.9

L;L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-5.3

.;.;D

REVEL

Benign

0.085

Sift

Uncertain

0.0010

.;.;D

Sift4G

Uncertain

0.0050

.;.;D

Polyphen

1.0

D;D;D

Vest4

0.54

MutPred

0.71

Gain of disorder (P = 0.0211);Gain of disorder (P = 0.0211);Gain of disorder (P = 0.0211);

MVP

0.38

MPC

0.099

ClinPred

0.99

GERP RS

3.3

Varity_R

0.77

gMVP

0.11

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over