7-144259081-A-G

Variant names:

• chr7-144259081-A-G
• rs1327413221
• NM_001005328.2:c.548T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001005328.2(OR2A7):​c.548T>C​(p.Val183Ala) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000050 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2A7 NM_001005328.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.31
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.548T>C	p.Val183Ala	missense	Exon 2 of 2	NP_001005328.1	Q96R45
	ARHGEF34P	NR_033942.1		n.4119T>C		non_coding_transcript_exon	Exon 13 of 13
	ARHGEF35-AS1	NR_126022.1		n.494-21391A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2A7	ENST00000641841.1	MANE Select	c.548T>C	p.Val183Ala	missense	Exon 2 of 2	ENSP00000493320.1	Q96R45
	OR2A7	ENST00000493325.1	TSL:6	c.548T>C	p.Val183Ala	missense	Exon 1 of 1	ENSP00000420502.1	Q96R45
	ARHGEF35-AS1	ENST00000460955.5	TSL:4	n.494-21391A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD2 exomes AF: 0.00000413 AC: 1 AN: 242318 AF XY: 0.00000757

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000921

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000495 AC: 7 AN: 1413596 Hom.: 0 Cov.: 30 AF XY: 0.00000284 AC XY: 2 AN XY: 704944

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

African (AFR) AF: 0.00 AC: 0 AN: 32704

American (AMR) AF: 0.00 AC: 0 AN: 44244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25756

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.00 AC: 0 AN: 85462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00000655 AC: 7 AN: 1068128

Other (OTH) AF: 0.00 AC: 0 AN: 58754

⚠️ 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 Cov.: 20

Alfa AF: 0.00 Hom.: 0

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	0.18
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.0042	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.3
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.47		Loss of stability (P = 0.0421)
MVP		0.67
ClinPred		0.94	D
GERP RS		3.1
Varity_R		0.43
gMVP		0.051
Mutation Taster		=98/2	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: rs1327413221; hg19: chr7-143956174;