chr7-144259414-T-C

Variant names:

Variant summary

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

The NM_001005328.2(OR2A7):c.215A>G(p.Tyr72Cys) 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 0.000053 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000054 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR2A7
NM_001005328.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0990

Publications

1 publications found

Variant links:

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]

OR2A7 links:

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

ARHGEF34P links:

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

ARHGEF35-AS1 links:

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

OR2A1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.11826491).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR2A7	NM_001005328.2	MANE Select	c.215A>G	p.Tyr72Cys	missense	Exon 2 of 2	NP_001005328.1	Q96R45
ARHGEF34P	NR_033942.1		n.3786A>G		non_coding_transcript_exon	Exon 13 of 13
ARHGEF35-AS1	NR_126022.1		n.494-21058T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR2A7	ENST00000641841.1	MANE Select	c.215A>G	p.Tyr72Cys	missense	Exon 2 of 2	ENSP00000493320.1	Q96R45
OR2A7	ENST00000493325.1	TSL:6	c.215A>G	p.Tyr72Cys	missense	Exon 1 of 1	ENSP00000420502.1	Q96R45
ARHGEF35-AS1	ENST00000460955.5	TSL:4	n.494-21058T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000533

AC:

AN:

131426

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000297

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000781

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00714

Gnomad NFE

AF:

0.0000323

Gnomad OTH

AF:

0.000584

GnomAD2 exomes

AF:

0.0000629

AC:

AN:

222640

AF XY:

0.0000578

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000126

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000912

Gnomad OTH exome

AF:

0.000179

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000540

AC:

AN:

1277770

Hom.:

Cov.:

AF XY:

0.0000498

AC XY:

AN XY:

642290

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

28288

American (AMR)

AF:

0.000188

AC:

AN:

42588

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24654

East Asian (EAS)

AF:

0.00

AC:

AN:

39052

South Asian (SAS)

AF:

0.00

AC:

AN:

81536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51574

Middle Eastern (MID)

AF:

0.000192

AC:

AN:

5198

European-Non Finnish (NFE)

AF:

0.0000463

AC:

AN:

950726

Other (OTH)

AF:

0.000295

AC:

AN:

54154

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.366

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000532

AC:

AN:

131544

Hom.:

Cov.:

AF XY:

0.0000789

AC XY:

AN XY:

63374

show subpopulations

African (AFR)

AF:

0.0000296

AC:

AN:

33832

American (AMR)

AF:

0.0000781

AC:

AN:

12812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3182

East Asian (EAS)

AF:

0.00

AC:

AN:

4722

South Asian (SAS)

AF:

0.00

AC:

AN:

3812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8532

Middle Eastern (MID)

AF:

0.00775

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.0000323

AC:

AN:

61824

Other (OTH)

AF:

0.000577

AC:

AN:

1734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.404

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000288

Hom.:

ExAC

AF:

0.0000420

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.019

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.036

M_CAP

Benign

0.0032

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.5

PhyloP100

0.099

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-7.7

REVEL

Benign

0.060

Sift

Uncertain

0.026

Sift4G

Uncertain

0.030

Polyphen

0.40

Vest4

0.42

MutPred

0.44

Gain of catalytic residue at I70 (P = 0.1164)

MVP

0.20

ClinPred

0.12

GERP RS

0.50

PromoterAI

0.0061

Neutral

(source)

Varity_R

0.16

gMVP

0.29

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over