NM_001005328.2:c.155C>G

Variant names:

• chr7-144259474-G-C
• rs776485163
• NM_001005328.2:c.155C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005328.2(OR2A7):​c.155C>G​(p.Ser52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 20)
  • Exomes 𝑓: 0.00021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2A7 NM_001005328.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0320
• Publications: 0 publications found

Genes affected

OR2A7 (HGNC:8234): (olfactory receptor family 2 subfamily A 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]

ARHGEF34P (HGNC:38086): (Rho guanine nucleotide exchange factor 34, pseudogene)

ARHGEF35-AS1 (HGNC:41292): (ARHGEF35 antisense RNA 1)

OR2A1-AS1 (HGNC:49168): (OR2A1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062807202).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005328.2. 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
	OR2A7	NM_001005328.2	MANE Select	c.155C>G	p.Ser52Cys	missense	Exon 2 of 2	NP_001005328.1	Q96R45
	ARHGEF34P	NR_033942.1		n.3726C>G		non_coding_transcript_exon	Exon 13 of 13
	ARHGEF35-AS1	NR_126022.1		n.494-20998G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2A7	ENST00000641841.1	MANE Select	c.155C>G	p.Ser52Cys	missense	Exon 2 of 2	ENSP00000493320.1	Q96R45
	OR2A7	ENST00000493325.1	TSL:6	c.155C>G	p.Ser52Cys	missense	Exon 1 of 1	ENSP00000420502.1	Q96R45
	ARHGEF35-AS1	ENST00000460955.5	TSL:4	n.494-20998G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000380 AC: 52 AN: 136740 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.000111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000829

Gnomad ASJ AF: 0.00469

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000243

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0113

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.00165

GnomAD2 exomes AF: 0.000346 AC: 85 AN: 245476 AF XY: 0.000367

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000383

Gnomad ASJ exome AF: 0.00445

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000162

Gnomad OTH exome AF: 0.000835

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000210 AC: 300 AN: 1430366 Hom.: 0 Cov.: 30 AF XY: 0.000219 AC XY: 156 AN XY: 713148

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000123 AC: 4 AN: 32416

American (AMR) AF: 0.000431 AC: 19 AN: 44070

Ashkenazi Jewish (ASJ) AF: 0.00352 AC: 89 AN: 25264

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.000199 AC: 17 AN: 85430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53194

Middle Eastern (MID) AF: 0.00342 AC: 19 AN: 5548

European-Non Finnish (NFE) AF: 0.000118 AC: 128 AN: 1085780

Other (OTH) AF: 0.000407 AC: 24 AN: 59034

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000380 AC: 52 AN: 136818 Hom.: 0 Cov.: 20 AF XY: 0.000454 AC XY: 30 AN XY: 66014

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000111 AC: 4 AN: 36174

American (AMR) AF: 0.000828 AC: 11 AN: 13278

Ashkenazi Jewish (ASJ) AF: 0.00469 AC: 15 AN: 3200

East Asian (EAS) AF: 0.00 AC: 0 AN: 4750

South Asian (SAS) AF: 0.000244 AC: 1 AN: 4102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8864

Middle Eastern (MID) AF: 0.0121 AC: 3 AN: 248

European-Non Finnish (NFE) AF: 0.000236 AC: 15 AN: 63484

Other (OTH) AF: 0.00163 AC: 3 AN: 1844

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00277 Hom.: 0

ExAC AF: 0.000901 AC: 109

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	Benign	0.076
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	17
DANN	Benign	0.74
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.037	N
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.032
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.022
Sift	Benign	0.20	T
Sift4G	Benign	0.12	T
Polyphen		0.0060	B
Vest4		0.14
MutPred		0.52		Loss of catalytic residue at S52 (P = 0.1789)
MVP		0.22
ClinPred		0.0081	T
GERP RS		1.0
PromoterAI		-0.0046	Neutral
Varity_R		0.067
gMVP		0.12
Mutation Taster		=97/3	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: rs776485163; hg19: chr7-143956567; COSMIC: COSV71827147; COSMIC: COSV71827147;