chr1-247921291-C-A

Variant names:

• chr1-247921291-C-A
• rs757258964
• NM_001005522.2:c.274C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005522.2(OR2T8):​c.274C>A​(p.Arg92Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R92C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 15)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T8 NM_001005522.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 4 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.057621747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2T8	NM_001005522.2	c.274C>A	p.Arg92Ser	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.274C>A	p.Arg92Ser	missense_variant	Exon 2 of 2		NM_001005522.2	ENSP00000493286.1

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD2 exomes AF: 0.00000709 AC: 1 AN: 141052 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: 0.0000845

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: 8.74e-7 AC: 1 AN: 1144462 Hom.: 0 Cov.: 20 AF XY: 0.00000174 AC XY: 1 AN XY: 575884

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26604

American (AMR) AF: 0.00 AC: 0 AN: 36064

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21596

East Asian (EAS) AF: 0.0000278 AC: 1 AN: 36024

South Asian (SAS) AF: 0.00 AC: 0 AN: 69282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3476

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 851822

Other (OTH) AF: 0.00 AC: 0 AN: 49496

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 15

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.2
DANN	Benign	0.85
DEOGEN2	Benign	0.0016	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.45	.;T
M_CAP	Benign	0.00079	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.70	N;N
PhyloP100		-1.7
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.14	.;N
REVEL	Benign	0.024
Sift	Benign	0.21	.;T
Sift4G	Benign	0.072	.;T
Polyphen		0.0030	B;B
Vest4		0.14
MutPred		0.58		Loss of methylation at R92 (P = 0.035);Loss of methylation at R92 (P = 0.035);
MVP		0.13
ClinPred		0.041	T
GERP RS		-1.8
Varity_R		0.074
gMVP		0.092
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs757258964; hg19: chr1-248084593; COSMIC: COSV60662108; COSMIC: COSV60662108;