7-144318290-A-C

Position:

• chr7-144318290-A-C

Variant summary

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

The NM_001005287.2(OR2A1):​c.166A>C​(p.Thr56Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., cov: 18)
  • Exomes 𝑓: 0.0019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2A1 NM_001005287.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05

Genes affected

OR2A1 (HGNC:8229): (olfactory receptor family 2 subfamily A member 1) 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]

ENSG00000284644 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2A1	NM_001005287.2	c.166A>C	p.Thr56Pro	missense_variant	2/2	ENST00000641044.2	NP_001005287.1
OR2A1	XM_047420323.1	c.166A>C	p.Thr56Pro	missense_variant	2/2		XP_047276279.1
OR2A1-AS1	NR_126023.1	n.494-6586T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2A1	ENST00000641044.2	c.166A>C	p.Thr56Pro	missense_variant	2/2		NM_001005287.2	ENSP00000493454.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 5 AN: 140262 Hom.: 0 Cov.: 18 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000216

Gnomad SAS AF: 0.000455

Gnomad FIN AF: 0.000107

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000156

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00188 AC: 2395 AN: 1273038 Hom.: 0 Cov.: 23 AF XY: 0.00177 AC XY: 1135 AN XY: 642032

Gnomad4 AFR exome AF: 0.00139

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000559

Gnomad4 EAS exome AF: 0.000179

Gnomad4 SAS exome AF: 0.000507

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00232

Gnomad4 OTH exome AF: 0.00186

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000356 AC: 5 AN: 140342 Hom.: 0 Cov.: 18 AF XY: 0.0000589 AC XY: 4 AN XY: 67900

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000217

Gnomad4 SAS AF: 0.000455

Gnomad4 FIN AF: 0.000107

Gnomad4 NFE AF: 0.0000156

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 04, 2024

The c.166A>C (p.T56P) alteration is located in exon 1 (coding exon 1) of the OR2A1 gene. This alteration results from a A to C substitution at nucleotide position 166, causing the threonine (T) at amino acid position 56 to be replaced by a proline (P). 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	0.12
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T;T
Eigen	Benign	0.042
Eigen_PC	Benign	-0.096
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.53	.;T
M_CAP	Benign	0.0018	T
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M;M
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-3.8	.;D
REVEL	Benign	0.13
Sift	Uncertain	0.0010	.;D
Sift4G	Pathogenic	0.0010	.;D
Vest4		0.52
MutPred		0.70		Gain of glycosylation at P57 (P = 0.1204);Gain of glycosylation at P57 (P = 0.1204);
MVP		0.48
ClinPred		0.96	D
GERP RS		1.6
Varity_R		0.90
gMVP		0.47

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: rs767052326; hg19: chr7-144015383;