1-248180512-A-G

Variant names:

• chr1-248180512-A-G
• rs568153469
• NM_001004688.2:c.527A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004688.2(OR2M2):​c.527A>G​(p.His176Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000793 in 1,613,876 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000081 (1 hom.)
• Consequence: OR2M2 NM_001004688.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.04
• Publications: 1 publications found

Genes affected

OR2M2 (HGNC:8268): (olfactory receptor family 2 subfamily M 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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18960258).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004688.2. 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
	OR2M2	NM_001004688.2	MANE Select	c.527A>G	p.His176Arg	missense	Exon 2 of 2	NP_001004688.1	A0A126GWI7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2M2	ENST00000641836.1	MANE Select	c.527A>G	p.His176Arg	missense	Exon 2 of 2	ENSP00000493201.1	Q96R28
	OR2M2	ENST00000641211.1		c.527A>G	p.His176Arg	missense	Exon 3 of 3	ENSP00000492974.1	Q96R28

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000119 AC: 30 AN: 251148 AF XY: 0.000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000970

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.0000807 AC: 118 AN: 1461642 Hom.: 1 Cov.: 72 AF XY: 0.0000963 AC XY: 70 AN XY: 727132

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.0000895 AC: 4 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5762

European-Non Finnish (NFE) AF: 0.0000576 AC: 64 AN: 1111818

Other (OTH) AF: 0.000199 AC: 12 AN: 60378

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74454

African (AFR) AF: 0.0000241 AC: 1 AN: 41528

American (AMR) AF: 0.000131 AC: 2 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000614 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.000123 AC: 15

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.014
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.00035	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		3.0
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-7.4	D
REVEL	Benign	0.033
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.96	D
Vest4		0.30
MutPred		0.53		Gain of phosphorylation at S171 (P = 0.1488)
MVP		0.30
MPC		0.50
ClinPred		0.36	T
GERP RS		1.9
Varity_R		0.65
gMVP		0.078
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs568153469; hg19: chr1-248343814; COSMIC: COSV100677184;