chr1-248453117-C-A

Position:

• chr1-248453117-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2 BP4_Strong BP6_Very_Strong BS1

The NM_001004136.2(OR2T2):​c.320C>A​(p.Thr107Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,602,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00036 (0 hom.)
• Consequence: OR2T2 NM_001004136.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.450

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 -14 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0027781725).
• BP6: Variant 1-248453117-C-A is Benign according to our data. Variant chr1-248453117-C-A is described in ClinVar as [Benign]. Clinvar id is 784981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1732/146220) while in subpopulation AFR AF= 0.0465 (1671/35932). AF 95% confidence interval is 0.0446. There are 0 homozygotes in gnomad4. There are 847 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T2	NM_001004136.2	c.320C>A	p.Thr107Asn	missense_variant	4/4	ENST00000641925.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T2	ENST00000641925.2	c.320C>A	p.Thr107Asn	missense_variant	4/4		NM_001004136.2	P1
OR2T2	ENST00000642130.1	c.320C>A	p.Thr107Asn	missense_variant	3/3			P1

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1732 AN: 146126 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00339

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00149

GnomAD3 exomes AF: 0.00551 AC: 1374 AN: 249144 Hom.: 0 AF XY: 0.00427 AC XY: 576 AN XY: 134930

Gnomad AFR exome AF: 0.0823

Gnomad AMR exome AF: 0.00442

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.00344

GnomAD4 exome AF: 0.000362 AC: 528 AN: 1456558 Hom.: 0 Cov.: 34 AF XY: 0.000326 AC XY: 236 AN XY: 724928

Gnomad4 AFR exome AF: 0.0154

Gnomad4 AMR exome AF: 0.000384

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.000602

GnomAD4 genome AF: 0.0118 AC: 1732 AN: 146220 Hom.: 0 Cov.: 28 AF XY: 0.0118 AC XY: 847 AN XY: 71534

Gnomad4 AFR AF: 0.0465

Gnomad4 AMR AF: 0.00345

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000589

Gnomad4 OTH AF: 0.00148

Alfa AF: 0.00363 Hom.: 1

ESP6500AA AF: 0.0152 AC: 67

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0113 AC: 1373

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 02, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T;T;T
Eigen	Benign	-0.011
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.099	N
MetaRNN	Benign	0.0028	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.8	M;M;M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.9	.;.;D
REVEL	Benign	0.084
Sift	Uncertain	0.015	.;.;D
Sift4G	Uncertain	0.011	.;.;D
Polyphen		1.0	D;D;D
Vest4		0.16
MPC		2.7
ClinPred		0.048	T
GERP RS		3.6
Varity_R		0.18
gMVP		0.25

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: rs149125804; hg19: chr1-248616418; COSMIC: COSV99048625;