5-181155106-A-G

Variant names:

• chr5-181155106-A-G
• rs761504979
• NM_206880.2:c.164A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_206880.2(OR2V2):​c.164A>G​(p.His55Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,613,732 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00091 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: OR2V2 NM_206880.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49

Genes affected

OR2V2 (HGNC:15341): (olfactory receptor family 2 subfamily V 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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.010656714).
• BP6: Variant 5-181155106-A-G is Benign according to our data. Variant chr5-181155106-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3411025.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2V2	NM_206880.2	c.164A>G	p.His55Arg	missense_variant	Exon 2 of 2	ENST00000641492.1	NP_996763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2V2	ENST00000641492.1	c.164A>G	p.His55Arg	missense_variant	Exon 2 of 2		NM_206880.2	ENSP00000493207.1
OR2V2	ENST00000641791.1	c.164A>G	p.His55Arg	missense_variant	Exon 3 of 3			ENSP00000493017.1

Frequencies

GnomAD3 genomes AF: 0.000909 AC: 138 AN: 151840 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000960

GnomAD3 exomes AF: 0.0000875 AC: 22 AN: 251488 Hom.: 0 AF XY: 0.0000441 AC XY: 6 AN XY: 135918

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000356 AC: 52 AN: 1461774 Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22 AN XY: 727192

Gnomad4 AFR exome AF: 0.00114

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.000133

GnomAD4 genome AF: 0.000908 AC: 138 AN: 151958 Hom.: 1 Cov.: 32 AF XY: 0.000781 AC XY: 58 AN XY: 74282

Gnomad4 AFR AF: 0.00317

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000950

Alfa AF: 0.000480 Hom.: 0

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 20, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.052
DANN	Benign	0.13
DEOGEN2	Benign	0.0025	T;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.33	.;.;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.011	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.65	N;N;N
PrimateAI	Benign	0.18	T
PROVEAN	Benign	1.9	.;.;N
REVEL	Benign	0.028
Sift	Benign	1.0	.;.;T
Sift4G	Benign	1.0	.;.;T
Polyphen		0.0	B;B;B
Vest4		0.033
MVP		0.11
MPC		0.086
ClinPred		0.013	T
GERP RS		-0.61
Varity_R		0.037
gMVP		0.058

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: rs761504979; hg19: chr5-180582106;