7-144074638-G-T

Position:

• chr7-144074638-G-T

Variant summary

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

The NM_001386096.1(OR2A25):​c.419G>T​(p.Cys140Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OR2A25 NM_001386096.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.26

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2A25	NM_001386096.1	c.419G>T	p.Cys140Phe	missense_variant	2/2	ENST00000641663.1	NP_001373025.1
OR2A25	NM_001004488.2	c.419G>T	p.Cys140Phe	missense_variant	2/2		NP_001004488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2A25	ENST00000641663.1	c.419G>T	p.Cys140Phe	missense_variant	2/2		NM_001386096.1	ENSP00000493343.1
OR2A25	ENST00000408898.2	c.419G>T	p.Cys140Phe	missense_variant	1/1	6		ENSP00000386167.2
OR2A25	ENST00000641441.1	c.419G>T	p.Cys140Phe	missense_variant	2/2			ENSP00000493159.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.419G>T (p.C140F) alteration is located in exon 1 (coding exon 1) of the OR2A25 gene. This alteration results from a G to T substitution at nucleotide position 419, causing the cysteine (C) at amino acid position 140 to be replaced by a phenylalanine (F). 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	0.19
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T;T;T
Eigen	Uncertain	0.41
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.72	.;.;T
M_CAP	Benign	0.0040	T
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	3.7	H;H;H
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-11	.;.;D
REVEL	Benign	0.13
Sift	Pathogenic	0.0	.;.;D
Sift4G	Uncertain	0.019	.;.;D
Polyphen		0.98	D;D;D
Vest4		0.57
MutPred		0.54		Loss of ubiquitination at K138 (P = 0.1381);Loss of ubiquitination at K138 (P = 0.1381);Loss of ubiquitination at K138 (P = 0.1381);
MVP		0.70
MPC		0.095
ClinPred		1.0	D
GERP RS		2.8
Varity_R		0.88
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-143771731;