dbSNP rs3129034: OR2H2:p.Leu30Ile (chr6-29588032-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007160.4(OR2H2):c.88C>A(p.Leu30Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR2H2
NM_007160.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18

Publications

24 publications found

Variant links:

Genes affected

OR2H2 (HGNC:8253): (olfactory receptor family 2 subfamily H 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]

OR2H2 links:

GABBR1 (HGNC:4070): (gamma-aminobutyric acid type B receptor subunit 1) This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy. Alternative splicing generates multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jan 2016]

GABBR1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with language delay and variable cognitive abnormalities
Inheritance: AD Classification: MODERATE Submitted by: G2P

GABBR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07506147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2H2	NM_007160.4 link	c.88C>A	p.Leu30Ile	missense_variant	Exon 2 of 2	ENST00000641840.1	NP_009091.3	O95918A0A1U9X844

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR2H2	ENST00000641840.1 link	c.88C>A	p.Leu30Ile	missense_variant	Exon 2 of 2		NM_007160.4	ENSP00000492959.1	O95918
OR2H2	ENST00000383640.4 link	c.88C>A	p.Leu30Ile	missense_variant	Exon 1 of 1	6		ENSP00000373136.2	O95918
GABBR1	ENST00000355973.7 link	c.*2+15509G>T		intron_variant	Intron 18 of 18	2		ENSP00000348248.3	Q9UBS5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

854498

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

449524

African (AFR)

AF:

0.00

AC:

AN:

23308

American (AMR)

AF:

0.00

AC:

AN:

44016

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22290

East Asian (EAS)

AF:

0.00

AC:

AN:

37254

South Asian (SAS)

AF:

0.00

AC:

AN:

74636

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4632

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

555516

Other (OTH)

AF:

0.00

AC:

AN:

40660

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.7

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0074

T;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.17

M_CAP

Benign

0.0013

MetaRNN

Benign

0.075

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.9

M;M

PhyloP100

-1.2

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.4

.;N

REVEL

Benign

0.051

Sift

Benign

0.080

.;T

Sift4G

Uncertain

0.047

.;D

Polyphen

0.15

B;B

Vest4

0.17

MutPred

0.36

Gain of catalytic residue at L35 (P = 0.0424);Gain of catalytic residue at L35 (P = 0.0424);

MVP

0.12

MPC

0.25

ClinPred

0.16

GERP RS

0.68

Varity_R

0.071

gMVP

0.066

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over