1-247921551-G-C

Variant names:

• chr1-247921551-G-C
• rs776204302
• NM_001005522.2:c.534G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005522.2(OR2T8):​c.534G>C​(p.Glu178Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 9)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T8 NM_001005522.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.95
• Publications: 1 publications found

Genes affected

OR2T8 (HGNC:15020): (olfactory receptor family 2 subfamily T member 8) 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16668838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2T8	NM_001005522.2	c.534G>C	p.Glu178Asp	missense_variant	Exon 2 of 2	ENST00000641945.2	NP_001005522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2T8	ENST00000641945.2	c.534G>C	p.Glu178Asp	missense_variant	Exon 2 of 2		NM_001005522.2	ENSP00000493286.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 67952 Hom.: 0 Cov.: 9

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000414 AC: 1 AN: 241380 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.12e-7 AC: 1 AN: 1403964 Hom.: 0 Cov.: 38 AF XY: 0.00000143 AC XY: 1 AN XY: 699510

African (AFR) AF: 0.0000302 AC: 1 AN: 33088

American (AMR) AF: 0.00 AC: 0 AN: 43398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 85524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4010

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1061986

Other (OTH) AF: 0.00 AC: 0 AN: 58556

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 67952 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 30408

African (AFR) AF: 0.00 AC: 0 AN: 18854

American (AMR) AF: 0.00 AC: 0 AN: 4852

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1740

East Asian (EAS) AF: 0.00 AC: 0 AN: 3328

South Asian (SAS) AF: 0.00 AC: 0 AN: 1990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 242

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 31952

Other (OTH) AF: 0.00 AC: 0 AN: 854

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.534G>C (p.E178D) alteration is located in exon 1 (coding exon 1) of the OR2T8 gene. This alteration results from a G to C substitution at nucleotide position 534, causing the glutamic acid (E) at amino acid position 178 to be replaced by an aspartic acid (D). 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	0.24
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0066	T;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.0059	N
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.00062	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.10	N;N
PhyloP100		-2.9
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	.;N
REVEL	Benign	0.076
Sift	Benign	0.31	.;T
Sift4G	Benign	0.29	.;T
Polyphen		0.22	B;B
Vest4		0.099
MutPred		0.64		Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);
MVP		0.39
ClinPred		0.28	T
GERP RS		1.4
Varity_R		0.071
gMVP		0.094
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs776204302; hg19: chr1-248084853;