7-144318288-A-C

Position:

• chr7-144318288-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001005287.2(OR2A1):​c.164A>C​(p.His55Pro) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 18)
  • Exomes 𝑓: 0.0057 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2A1 NM_001005287.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96

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 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2A1	NM_001005287.2	c.164A>C	p.His55Pro	missense_variant	2/2	ENST00000641044.2	NP_001005287.1
OR2A1	XM_047420323.1	c.164A>C	p.His55Pro	missense_variant	2/2		XP_047276279.1
OR2A1-AS1	NR_126023.1	n.494-6584T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2A1	ENST00000641044.2	c.164A>C	p.His55Pro	missense_variant	2/2		NM_001005287.2	ENSP00000493454.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 29 AN: 140630 Hom.: 0 Cov.: 18 FAILED QC

Gnomad AFR AF: 0.0000528

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000147

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000435

Gnomad SAS AF: 0.000920

Gnomad FIN AF: 0.000424

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000233

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00571 AC: 7249 AN: 1269288 Hom.: 0 Cov.: 23 AF XY: 0.00533 AC XY: 3411 AN XY: 640252

Gnomad4 AFR exome AF: 0.00440

Gnomad4 AMR exome AF: 0.000432

Gnomad4 ASJ exome AF: 0.00276

Gnomad4 EAS exome AF: 0.00282

Gnomad4 SAS exome AF: 0.00162

Gnomad4 FIN exome AF: 0.00146

Gnomad4 NFE exome AF: 0.00683

Gnomad4 OTH exome AF: 0.00543

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000206 AC: 29 AN: 140714 Hom.: 0 Cov.: 18 AF XY: 0.000294 AC XY: 20 AN XY: 68064

Gnomad4 AFR AF: 0.0000527

Gnomad4 AMR AF: 0.000147

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000436

Gnomad4 SAS AF: 0.000920

Gnomad4 FIN AF: 0.000424

Gnomad4 NFE AF: 0.000233

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

Mar 18, 2024

The c.164A>C (p.H55P) 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 164, causing the histidine (H) at amino acid position 55 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	0.17
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.030	T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.49	.;T
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Pathogenic	3.9	H;H
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-7.6	.;D
REVEL	Benign	0.26
Sift	Uncertain	0.0030	.;D
Sift4G	Pathogenic	0.0010	.;D
Vest4		0.79
MutPred		0.72		Gain of glycosylation at H55 (P = 0.0717);Gain of glycosylation at H55 (P = 0.0717);
MVP		0.67
ClinPred		0.99	D
GERP RS		3.0
Varity_R		0.93
gMVP		0.44

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: rs533955110; hg19: chr7-144015381;