1-248522041-A-G

Variant names:

• chr1-248522041-A-G
• rs1664300541
• NM_001013355.2:c.395A>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001013355.2(OR2G6):​c.395A>G​(p.Tyr132Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR2G6 NM_001013355.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.24

Genes affected

OR2G6 (HGNC:27019): (olfactory receptor family 2 subfamily G member 6) 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]

LOC105373277 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.913

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2G6	NM_001013355.2	c.395A>G	p.Tyr132Cys	missense_variant	Exon 2 of 2	ENST00000641804.1	NP_001013373.1
LOC105373277	XR_002958498.2	n.104+14640T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2G6	ENST00000641804.1	c.395A>G	p.Tyr132Cys	missense_variant	Exon 2 of 2		NM_001013355.2	ENSP00000493355.1
OR2G6	ENST00000641501.1	c.395A>G	p.Tyr132Cys	missense_variant	Exon 2 of 2			ENSP00000492940.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 29, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.395A>G (p.Y132C) alteration is located in exon 1 (coding exon 1) of the OR2G6 gene. This alteration results from a A to G substitution at nucleotide position 395, causing the tyrosine (Y) at amino acid position 132 to be replaced by a cysteine (C). 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	Uncertain	0.50
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T;T;T
Eigen	Uncertain	0.46
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	.;.;D
M_CAP	Benign	0.0021	T
MetaRNN	Pathogenic	0.91	D;D;D
MetaSVM	Uncertain	-0.0073	T
MutationAssessor	Pathogenic	3.5	H;H;H
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-8.9	.;.;D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	.;.;D
Sift4G	Pathogenic	0.0	.;.;D
Polyphen		1.0	D;D;D
Vest4		0.69
MutPred		0.65		Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP		0.50
MPC		0.019
ClinPred		1.0	D
GERP RS		3.5
Varity_R		0.78
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1664300541; hg19: chr1-248685342;