1-248521723-T-G

Variant names:

• chr1-248521723-T-G
• NM_001013355.2:c.77T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013355.2(OR2G6):​c.77T>G​(p.Phe26Cys) 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. 15/21 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: OR2G6 NM_001013355.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.687

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06414428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2G6	NM_001013355.2	c.77T>G	p.Phe26Cys	missense_variant	Exon 2 of 2	ENST00000641804.1	NP_001013373.1
LOC105373277	XR_002958498.2	n.104+14958A>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2G6	ENST00000641804.1	c.77T>G	p.Phe26Cys	missense_variant	Exon 2 of 2		NM_001013355.2	ENSP00000493355.1
OR2G6	ENST00000641501.1	c.77T>G	p.Phe26Cys	missense_variant	Exon 2 of 2			ENSP00000492940.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.77T>G (p.F26C) alteration is located in exon 1 (coding exon 1) of the OR2G6 gene. This alteration results from a T to G substitution at nucleotide position 77, causing the phenylalanine (F) at amino acid position 26 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	Benign	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.0083	T;T;T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.73	.;.;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.064	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	M;M;M
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.23	.;.;N
REVEL	Benign	0.047
Sift	Uncertain	0.016	.;.;D
Sift4G	Uncertain	0.025	.;.;D
Polyphen		0.0	B;B;B
Vest4		0.16
MutPred		0.30		Gain of catalytic residue at L27 (P = 0.012);Gain of catalytic residue at L27 (P = 0.012);Gain of catalytic residue at L27 (P = 0.012);
MVP		0.43
MPC		0.0074
ClinPred		0.082	T
GERP RS		1.4
Varity_R		0.12
gMVP		0.098

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-248685024;