1-248038499-C-A

Variant names:

• chr1-248038499-C-A
• NM_001385855.1:c.232C>A

Variant summary

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

The NM_001385855.1(OR2L2):​c.232C>A​(p.Pro78Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR2L2 NM_001385855.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.95

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

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 rank	MANE	Protein	UniProt
OR2L2	NM_001385855.1	c.232C>A	p.Pro78Thr	missense_variant	Exon 3 of 3	ENST00000641771.1	NP_001372784.1
OR2L2	NM_001004686.3	c.232C>A	p.Pro78Thr	missense_variant	Exon 2 of 2		NP_001004686.1
OR2L13	NM_001304535.3	c.-18-60859C>A		intron_variant	Intron 1 of 1		NP_001291464.1
OR2L13	NM_175911.5	c.-143-60152C>A		intron_variant	Intron 1 of 2		NP_787107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2L2	ENST00000641771.1	c.232C>A	p.Pro78Thr	missense_variant	Exon 3 of 3		NM_001385855.1	ENSP00000493410.1
OR2L2	ENST00000366479.4	c.232C>A	p.Pro78Thr	missense_variant	Exon 1 of 1	6		ENSP00000355435.2
OR2L2	ENST00000642011.1	c.232C>A	p.Pro78Thr	missense_variant	Exon 2 of 2			ENSP00000493154.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.232C>A (p.P78T) alteration is located in exon 1 (coding exon 1) of the OR2L2 gene. This alteration results from a C to A substitution at nucleotide position 232, causing the proline (P) at amino acid position 78 to be replaced by a threonine (T). 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	Uncertain	0.45
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T;T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.086	N
LIST_S2	Uncertain	0.90	.;.;D
M_CAP	Benign	0.00075	T
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.9	H;H;H
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-7.5	.;.;D
REVEL	Benign	0.089
Sift	Pathogenic	0.0	.;.;D
Sift4G	Uncertain	0.0080	.;.;D
Polyphen		0.99	D;D;D
Vest4		0.49
MutPred		0.58		Loss of glycosylation at T75 (P = 0.0537);Loss of glycosylation at T75 (P = 0.0537);Loss of glycosylation at T75 (P = 0.0537);
MVP		0.27
MPC		0.088
ClinPred		0.69	D
GERP RS		0.96
Varity_R		0.59
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-248201801; COSMIC: COSV63560749;