chr1-248406784-G-C

Position:

• chr1-248406784-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030904.2(OR2T1):​c.637G>C​(p.Val213Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR2T1 NM_030904.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0750

Genes affected

OR2T1 (HGNC:8277): (olfactory receptor family 2 subfamily T member 1) 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T1	NM_030904.2	c.637G>C	p.Val213Leu	missense_variant	2/2	ENST00000642005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T1	ENST00000642005.1	c.637G>C	p.Val213Leu	missense_variant	2/2		NM_030904.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.790G>C (p.V264L) alteration is located in exon 1 (coding exon 1) of the OR2T1 gene. This alteration results from a G to C substitution at nucleotide position 790, causing the valine (V) at amino acid position 264 to be replaced by a leucine (L). 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	0.28
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	.;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.80	T;.
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.83	.;L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.5	.;N
REVEL	Benign	0.075
Sift	Uncertain	0.0020	.;D
Sift4G	Uncertain	0.0020	.;D
Polyphen		0.89	.;P
Vest4		0.13
MutPred		0.63		.;Loss of glycosylation at S262 (P = 0.2583);
MVP		0.37
MPC		0.059
ClinPred		0.45	T
GERP RS		1.6
Varity_R		0.29
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.35		Position offset: 34

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-248570085;