1-248453107-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2 BP4_Strong BP6_Moderate BA1

The NM_001004136.2(OR2T2):c.310C>T(p.Leu104Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 1,366,624 control chromosomes in the GnomAD database, including 4,140 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (1187 hom., cov: 32)
  • Exomes 𝑓: 0.050 (2953 hom.)
• Consequence: OR2T2 NM_001004136.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

Genes affected

OR2T2 (HGNC:14725): (olfactory receptor family 2 subfamily T 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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• PP2: Missense variant where missense usually causes diseases, OR2T2
• BP4: Computational evidence support a benign effect (MetaRNN=9.804666E-4).
• BP6: Variant 1-248453107-C-T is Benign according to our data. Variant chr1-248453107-C-T is described in ClinVar as [Benign]. Clinvar id is 767777.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T2	NM_001004136.2	c.310C>T	p.Leu104Phe	missense_variant	4/4	ENST00000641925.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T2	ENST00000641925.2	c.310C>T	p.Leu104Phe	missense_variant	4/4		NM_001004136.2	P1
OR2T2	ENST00000642130.1	c.310C>T	p.Leu104Phe	missense_variant	3/3			P1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 22608 AN: 110784 Hom.: 1184 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0889

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0772

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.0501 AC: 62906 AN: 1255752 Hom.: 2953 Cov.: 35 AF XY: 0.0538 AC XY: 33373 AN XY: 620166

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.0873

Gnomad4 ASJ exome AF: 0.0563

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.0295

Gnomad4 OTH exome AF: 0.0667

GnomAD4 genome AF: 0.204 AC: 22645 AN: 110872 Hom.: 1187 Cov.: 32 AF XY: 0.205 AC XY: 11073 AN XY: 54096

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.0889

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.143

Alfa AF: 0.275 Hom.: 116

ExAC AF: 0.327 AC: 39736

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 02, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	13
Dann	Benign	0.11
DEOGEN2	Benign	0.0097	T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.015	N
MetaRNN	Benign	0.00098	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.63	N;N;N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.27	T
Polyphen		0.0080	B;B;B
Vest4		0.059
MPC		1.6
ClinPred		0.0075	T
GERP RS		-0.64
Varity_R		0.036
gMVP		0.10

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: rs67700848; hg19: chr1-248616408; COSMIC: COSV61617638;