1-248323715-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001004691.1(OR2M7):​c.854T>C​(p.Leu285Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000146 in 1,613,484 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

OR2M7
NM_001004691.1 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.40
Variant links:
Genes affected
OR2M7 (HGNC:19594): (olfactory receptor family 2 subfamily M 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.19196197).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR2M7NM_001004691.1 linkc.854T>C p.Leu285Pro missense_variant Exon 1 of 1 ENST00000317965.3 NP_001004691.1 Q8NG81A0A126GVZ1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR2M7ENST00000317965.3 linkc.854T>C p.Leu285Pro missense_variant Exon 1 of 1 6 NM_001004691.1 ENSP00000324557.2 Q8NG81

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00173
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000216
AC:
54
AN:
250434
Hom.:
0
AF XY:
0.000303
AC XY:
41
AN XY:
135294
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000796
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00115
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000707
Gnomad OTH exome
AF:
0.000492
GnomAD4 exome
AF:
0.000153
AC:
223
AN:
1461150
Hom.:
2
Cov.:
37
AF XY:
0.000219
AC XY:
159
AN XY:
726872
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00172
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00136
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000297
Gnomad4 OTH exome
AF:
0.000232
GnomAD4 genome
AF:
0.0000853
AC:
13
AN:
152334
Hom.:
0
Cov.:
32
AF XY:
0.0000940
AC XY:
7
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00173
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000270
Hom.:
0
Bravo
AF:
0.0000604
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000222
AC:
27
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 03, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.854T>C (p.L285P) alteration is located in exon 1 (coding exon 1) of the OR2M7 gene. This alteration results from a T to C substitution at nucleotide position 854, causing the leucine (L) at amino acid position 285 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
21
DANN
Benign
0.94
DEOGEN2
Benign
0.065
T
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.62
D
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-0.75
T
MutationAssessor
Pathogenic
3.6
H
PrimateAI
Benign
0.20
T
PROVEAN
Pathogenic
-6.3
D
REVEL
Benign
0.18
Sift
Uncertain
0.0070
D
Sift4G
Uncertain
0.0060
D
Polyphen
0.34
B
Vest4
0.41
MVP
0.34
MPC
0.080
ClinPred
0.19
T
GERP RS
0.27
Varity_R
0.81
gMVP
0.33

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs371662956; hg19: chr1-248487017; API