chr7-144074811-G-C

Position:

• chr7-144074811-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001386096.1(OR2A25):​c.592G>C​(p.Val198Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR2A25 NM_001386096.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488

Genes affected

OR2A25 (HGNC:19562): (olfactory receptor family 2 subfamily A member 25) 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07391769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2A25	NM_001386096.1	c.592G>C	p.Val198Leu	missense_variant	2/2	ENST00000641663.1
OR2A25	NM_001004488.2	c.592G>C	p.Val198Leu	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2A25	ENST00000641663.1	c.592G>C	p.Val198Leu	missense_variant	2/2		NM_001386096.1	P1
OR2A25	ENST00000408898.2	c.592G>C	p.Val198Leu	missense_variant	1/1			P1
OR2A25	ENST00000641441.1	c.592G>C	p.Val198Leu	missense_variant	2/2			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000800 AC: 2 AN: 250012 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135604

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.81
DEOGEN2	Benign	0.0016	T;T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.036	N
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.074	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	-0.035	N;N;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.38	T
Polyphen		0.058	B;B;B
Vest4		0.058
MutPred		0.58		Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP		0.18
MPC		0.020
ClinPred		0.062	T
GERP RS		3.0
Varity_R		0.043
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs781424500; hg19: chr7-143771904;