1-248453367-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001004136.2(OR2T2):c.570C>T(p.Cys190=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0082 (40 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T2 NM_001004136.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.232

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-248453367-C-T is Benign according to our data. Variant chr1-248453367-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640254.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.232 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T2	NM_001004136.2	c.570C>T	p.Cys190=	synonymous_variant	4/4	ENST00000641925.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T2	ENST00000641925.2	c.570C>T	p.Cys190=	synonymous_variant	4/4		NM_001004136.2	P1
OR2T2	ENST00000642130.1	c.570C>T	p.Cys190=	synonymous_variant	3/3			P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 800 AN: 148538 Hom.: 0 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00309

Gnomad ASJ AF: 0.00290

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000700

Gnomad FIN AF: 0.00502

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00911

Gnomad OTH AF: 0.00585

GnomAD3 exomes AF: 0.00586 AC: 1398 AN: 238712 Hom.: 10 AF XY: 0.00589 AC XY: 762 AN XY: 129292

Gnomad AFR exome AF: 0.00149

Gnomad AMR exome AF: 0.00287

Gnomad ASJ exome AF: 0.00163

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000446

Gnomad FIN exome AF: 0.00586

Gnomad NFE exome AF: 0.0102

Gnomad OTH exome AF: 0.00530

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00820 AC: 11645 AN: 1419778 Hom.: 40 Cov.: 32 AF XY: 0.00795 AC XY: 5626 AN XY: 707774

Gnomad4 AFR exome AF: 0.00103

Gnomad4 AMR exome AF: 0.00299

Gnomad4 ASJ exome AF: 0.00280

Gnomad4 EAS exome AF: 0.0000260

Gnomad4 SAS exome AF: 0.000449

Gnomad4 FIN exome AF: 0.00618

Gnomad4 NFE exome AF: 0.00979

Gnomad4 OTH exome AF: 0.00760

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00538 AC: 799 AN: 148644 Hom.: 0 Cov.: 27 AF XY: 0.00526 AC XY: 381 AN XY: 72386

Gnomad4 AFR AF: 0.00130

Gnomad4 AMR AF: 0.00309

Gnomad4 ASJ AF: 0.00290

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000701

Gnomad4 FIN AF: 0.00502

Gnomad4 NFE AF: 0.00910

Gnomad4 OTH AF: 0.00579

Alfa AF: 0.00679 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

OR2T2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.1
Dann	Benign	0.33

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: rs144808604; hg19: chr1-248616668;