1-247965759-A-G

Position:

• chr1-247965759-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004491.2(OR2AK2):​c.383A>G​(p.His128Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR2AK2 NM_001004491.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.210

Genes affected

OR2AK2 (HGNC:19569): (olfactory receptor family 2 subfamily AK member 2) 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]

OR2L13 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15927577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2AK2	NM_001004491.2	c.383A>G	p.His128Arg	missense_variant	1/1	ENST00000366480.5
OR2L13	NM_001304535.3	c.-19+28375A>G		intron_variant
OR2L13	NM_175911.5	c.-144+28375A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2AK2	ENST00000366480.5	c.383A>G	p.His128Arg	missense_variant	1/1		NM_001004491.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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

Apr 26, 2023

The c.428A>G (p.H143R) alteration is located in exon 1 (coding exon 1) of the OR2AK2 gene. This alteration results from a A to G substitution at nucleotide position 428, causing the histidine (H) at amino acid position 143 to be replaced by an arginine (R). 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	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.4
DANN	Benign	0.78
DEOGEN2	Benign	0.0052	.;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.23	T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.0	.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
REVEL	Benign	0.042
Polyphen		0.0040	.;B
MutPred		0.68		.;Loss of loop (P = 0.2237);
MVP		0.13
MPC		0.034
ClinPred		0.048	T
GERP RS		3.0
Varity_R		0.11
gMVP		0.078

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: rs1660954729; hg19: chr1-248129061;