1-248038949-C-T

Variant names:

• chr1-248038949-C-T
• rs777771095
• NM_001385855.1:c.682C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385855.1(OR2L2):​c.682C>T​(p.His228Tyr) 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. 15/22 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. H228N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR2L2 NM_001385855.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.15
• Publications: 2 publications found

Genes affected

OR2L2 (HGNC:8266): (olfactory receptor family 2 subfamily L 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]

OR2L13 (HGNC:19578): (olfactory receptor family 2 subfamily L member 13) 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11402619).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385855.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2L2	NM_001385855.1	MANE Select	c.682C>T	p.His228Tyr	missense	Exon 3 of 3	NP_001372784.1	Q8NH16
	OR2L2	NM_001004686.3		c.682C>T	p.His228Tyr	missense	Exon 2 of 2	NP_001004686.1	Q8NH16
	OR2L13	NM_001304535.3		c.-18-60409C>T		intron	N/A	NP_001291464.1	Q8N349

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2L2	ENST00000641771.1	MANE Select	c.682C>T	p.His228Tyr	missense	Exon 3 of 3	ENSP00000493410.1	Q8NH16
	OR2L2	ENST00000366479.4	TSL:6	c.682C>T	p.His228Tyr	missense	Exon 1 of 1	ENSP00000355435.2	Q8NH16
	OR2L2	ENST00000642011.1		c.682C>T	p.His228Tyr	missense	Exon 2 of 2	ENSP00000493154.1	Q8NH16

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.8
DANN	Benign	0.78
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L
PhyloP100		-6.2
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.025
Sift	Benign	0.055	T
Sift4G	Uncertain	0.013	D
Polyphen		0.40	B
Vest4		0.15
MutPred		0.28		Loss of disorder (P = 0.0651)
MVP		0.22
MPC		0.016
ClinPred		0.45	T
GERP RS		-0.61
Varity_R		0.10
gMVP		0.061
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs777771095; hg19: chr1-248202251;