1-248323916-T-C

Variant names:

• chr1-248323916-T-C
• rs1444665060
• NM_001004691.1:c.653A>G

Variant summary

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

The NM_001004691.1(OR2M7):​c.653A>G​(p.Tyr218Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,810 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OR2M7 NM_001004691.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.99

Genes affected

OR2M7 (HGNC:19594): (olfactory receptor family 2 subfamily M member 7) 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
OR2M7	NM_001004691.1	c.653A>G	p.Tyr218Cys	missense_variant	Exon 1 of 1	ENST00000317965.3	NP_001004691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2M7	ENST00000317965.3	c.653A>G	p.Tyr218Cys	missense_variant	Exon 1 of 1	6	NM_001004691.1	ENSP00000324557.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251076 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135682

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460810 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 726758

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.653A>G (p.Y218C) alteration is located in exon 1 (coding exon 1) of the OR2M7 gene. This alteration results from a A to G substitution at nucleotide position 653, causing the tyrosine (Y) at amino acid position 218 to be replaced by a cysteine (C). 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	0.21
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.00052	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-8.3	D
REVEL	Benign	0.095
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.030	D
Polyphen		0.53	P
Vest4		0.44
MutPred		0.72		Loss of glycosylation at T216 (P = 0.0444);
MVP		0.31
MPC		0.19
ClinPred		0.99	D
GERP RS		1.6
Varity_R		0.65
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1444665060; hg19: chr1-248487218;