dbSNP rs2961135: OR2A25:p.Ala209Thr (chr7-144074844-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001386096.1(OR2A25):c.625G>A(p.Ala209Thr) 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 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OR2A25
NM_001386096.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.190

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07172346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2A25	NM_001386096.1 link	c.625G>A	p.Ala209Thr	missense_variant	Exon 2 of 2	ENST00000641663.1	NP_001373025.1
OR2A25	NM_001004488.2 link	c.625G>A	p.Ala209Thr	missense_variant	Exon 2 of 2		NP_001004488.1	A4D2G3A0A126GVV5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR2A25	ENST00000641663.1 link	c.625G>A	p.Ala209Thr	missense_variant	Exon 2 of 2		NM_001386096.1	ENSP00000493343.1	A4D2G3
OR2A25	ENST00000408898.2 link	c.625G>A	p.Ala209Thr	missense_variant	Exon 1 of 1	6		ENSP00000386167.2	A4D2G3
OR2A25	ENST00000641441.1 link	c.625G>A	p.Ala209Thr	missense_variant	Exon 2 of 2			ENSP00000493159.1	A4D2G3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112000

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.00031

T;T;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.16

.;.;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.072

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.57

N;N;N

PhyloP100

-0.19

PrimateAI

Benign

0.32

PROVEAN

Benign

0.0

.;.;N

REVEL

Benign

0.085

Sift

Uncertain

0.0010

.;.;D

Sift4G

Uncertain

0.032

.;.;D

Polyphen

0.0010

B;B;B

Vest4

0.062

MutPred

0.48

Loss of stability (P = 0.078);Loss of stability (P = 0.078);Loss of stability (P = 0.078);

MVP

0.16

MPC

0.013

ClinPred

0.16

GERP RS

4.8

Varity_R

0.13

gMVP

0.094

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over