chr6-29588032-C-A

Variant names:

• chr6-29588032-C-A
• rs3129034
• NM_007160.4:c.88C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 24 publications found

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]

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

ACMG classification

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007160.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2H2	NM_007160.4	MANE Select	c.88C>A	p.Leu30Ile	missense	Exon 2 of 2	NP_009091.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2H2	ENST00000641840.1	MANE Select	c.88C>A	p.Leu30Ile	missense	Exon 2 of 2	ENSP00000492959.1
	OR2H2	ENST00000383640.4	TSL:6	c.88C>A	p.Leu30Ile	missense	Exon 1 of 1	ENSP00000373136.2
	GABBR1	ENST00000355973.7	TSL:2	c.*2+15509G>T		intron	N/A	ENSP00000348248.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 854498 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 449524

African (AFR) AF: 0.00 AC: 0 AN: 23308

American (AMR) AF: 0.00 AC: 0 AN: 44016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22290

East Asian (EAS) AF: 0.00 AC: 0 AN: 37254

South Asian (SAS) AF: 0.00 AC: 0 AN: 74636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4632

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 555516

Other (OTH) AF: 0.00 AC: 0 AN: 40660

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.17	N
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		-1.2
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.051
Sift	Benign	0.080	T
Sift4G	Uncertain	0.047	D
Polyphen		0.15	B
Vest4		0.17
MutPred		0.36		Gain of catalytic residue at L35 (P = 0.0424)
MVP		0.12
MPC		0.25
ClinPred		0.16	T
GERP RS		0.68
Varity_R		0.071
gMVP		0.066
Mutation Taster		=99/1	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: rs3129034; hg19: chr6-29555809;