rs2961135

Positions:

• chr7-144074844-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386096.1(OR2A25):​c.625G>C​(p.Ala209Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,613,616 control chromosomes in the GnomAD database, including 229,993 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.58 (25748 hom., cov: 31)
  • Exomes 𝑓: 0.53 (204245 hom.)
• Consequence: OR2A25 NM_001386096.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.7080066E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2A25	NM_001386096.1	c.625G>C	p.Ala209Pro	missense_variant	2/2	ENST00000641663.1	NP_001373025.1
OR2A25	NM_001004488.2	c.625G>C	p.Ala209Pro	missense_variant	2/2		NP_001004488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2A25	ENST00000641663.1	c.625G>C	p.Ala209Pro	missense_variant	2/2		NM_001386096.1	ENSP00000493343.1
OR2A25	ENST00000408898.2	c.625G>C	p.Ala209Pro	missense_variant	1/1	6		ENSP00000386167.2
OR2A25	ENST00000641441.1	c.625G>C	p.Ala209Pro	missense_variant	2/2			ENSP00000493159.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87415 AN: 151886 Hom.: 25712 Cov.: 31

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.577

GnomAD3 exomes AF: 0.570 AC: 142549 AN: 250024 Hom.: 41977 AF XY: 0.558 AC XY: 75669 AN XY: 135610

Gnomad AFR exome AF: 0.691

Gnomad AMR exome AF: 0.744

Gnomad ASJ exome AF: 0.448

Gnomad EAS exome AF: 0.660

Gnomad SAS exome AF: 0.529

Gnomad FIN exome AF: 0.551

Gnomad NFE exome AF: 0.512

Gnomad OTH exome AF: 0.558

GnomAD4 exome AF: 0.525 AC: 767701 AN: 1461612 Hom.: 204245 Cov.: 54 AF XY: 0.524 AC XY: 380853 AN XY: 727130

Gnomad4 AFR exome AF: 0.685

Gnomad4 AMR exome AF: 0.735

Gnomad4 ASJ exome AF: 0.449

Gnomad4 EAS exome AF: 0.640

Gnomad4 SAS exome AF: 0.526

Gnomad4 FIN exome AF: 0.552

Gnomad4 NFE exome AF: 0.508

Gnomad4 OTH exome AF: 0.538

GnomAD4 genome AF: 0.576 AC: 87509 AN: 152004 Hom.: 25748 Cov.: 31 AF XY: 0.579 AC XY: 43027 AN XY: 74270

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.571

Alfa AF: 0.517 Hom.: 6627

Bravo AF: 0.594

TwinsUK AF: 0.504 AC: 1867

ALSPAC AF: 0.526 AC: 2026

ESP6500AA AF: 0.693 AC: 2856

ESP6500EA AF: 0.514 AC: 4345

ExAC AF: 0.566 AC: 68520

Asia WGS AF: 0.615 AC: 2142 AN: 3478

EpiCase AF: 0.505

EpiControl AF: 0.512

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.2
DANN	Benign	0.47
DEOGEN2	Benign	0.00023	T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.10	.;.;T
MetaRNN	Benign	0.0000027	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.3	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	7.3	.;.;N
REVEL	Benign	0.063
Sift	Benign	1.0	.;.;T
Sift4G	Benign	1.0	.;.;T
Polyphen		0.0	B;B;B
Vest4		0.050
MPC		0.013
ClinPred		0.0032	T
GERP RS		4.8
Varity_R		0.091
gMVP		0.30

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

Other links and lift over

dbSNP: rs2961135; hg19: chr7-143771937; COSMIC: COSV68717253; COSMIC: COSV68717253;