chr7-144318263-C-G

Position:

• chr7-144318263-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005287.2(OR2A1):​c.139C>G​(p.Leu47Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 17)
  • Exomes 𝑓: 0.0000041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2A1 NM_001005287.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.02

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]

OR2A1-AS1 (HGNC:49168): (OR2A1 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.085407525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2A1	NM_001005287.2	c.139C>G	p.Leu47Val	missense_variant	2/2	ENST00000641044.2
OR2A1-AS1	NR_126023.1	n.494-6559G>C		intron_variant, non_coding_transcript_variant
OR2A1	XM_047420323.1	c.139C>G	p.Leu47Val	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2A1	ENST00000641044.2	c.139C>G	p.Leu47Val	missense_variant	2/2		NM_001005287.2	P1
OR2A1-AS1	ENST00000496968.5	n.296-6324G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000405 AC: 5 AN: 1234230 Hom.: 0 Cov.: 22 AF XY: 0.00000481 AC XY: 3 AN XY: 624100

Gnomad4 AFR exome AF: 0.000105

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: 0.0000378

GnomAD4 genome Cov.: 17

Bravo AF: 0.00000378

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

Jul 21, 2021

The c.139C>G (p.L47V) alteration is located in exon 1 (coding exon 1) of the OR2A1 gene. This alteration results from a C to G substitution at nucleotide position 139, causing the leucine (L) at amino acid position 47 to be replaced by a valine (V). 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	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.016	T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.60	.;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.95	L;L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.9	.;N
REVEL	Benign	0.030
Sift	Benign	0.13	.;T
Sift4G	Benign	0.18	.;T
Vest4		0.28
MutPred		0.47		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.18
ClinPred		0.057	T
GERP RS		0.58
Varity_R		0.15
gMVP		0.051

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: rs573150405; hg19: chr7-144015356;