9-135547246-C-A

Position:

• chr9-135547246-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014582.3(OBP2A):​c.275C>A​(p.Ala92Asp) variant causes a missense, splice region 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. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OBP2A NM_014582.3 missense, splice_region
• Scores: Splicing: ADA: 0.00008270
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.228

Genes affected

OBP2A (HGNC:23380): (odorant binding protein 2A) This gene encodes a small extracellular protein belonging to the lipocalin superfamily. The protein is thought to transport small, hydrophobic, volatile molecules or odorants through the nasal mucus to olfactory receptors, and may also function as a scavenger of highly concentrated or toxic odors. The protein is expressed as a monomer in the nasal mucus, and can bind diverse types of odorants with a higher affinity for aldehydes and fatty acids. This gene and a highly similar family member are located in a cluster of lipocalin genes on chromosome 9. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

OBP2A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34860277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OBP2A	NM_014582.3	c.275C>A	p.Ala92Asp	missense_variant, splice_region_variant	3/7	ENST00000371776.6	NP_055397.1
OBP2A	NM_001293189.2	c.275C>A	p.Ala92Asp	missense_variant, splice_region_variant	3/7		NP_001280118.1
OBP2A	NM_001293193.2	c.141C>A	p.Arg47Arg	splice_region_variant, synonymous_variant	2/6		NP_001280122.1
OBP2A	NR_120603.2	n.330C>A		splice_region_variant, non_coding_transcript_exon_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OBP2A	ENST00000371776.6	c.275C>A	p.Ala92Asp	missense_variant, splice_region_variant	3/7	1	NM_014582.3	ENSP00000360841.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

May 24, 2024

The c.275C>A (p.A92D) alteration is located in exon 3 (coding exon 3) of the OBP2A gene. This alteration results from a C to A substitution at nucleotide position 275, causing the alanine (A) at amino acid position 92 to be replaced by an aspartic acid (D). 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	Uncertain	0.40
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.018	.;.;T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.41	T;T;.;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	.;.;M;M
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-4.3	.;D;D;D
REVEL	Benign	0.076
Sift	Uncertain	0.0030	.;D;D;D
Sift4G	Uncertain	0.020	D;D;D;D
Polyphen		0.97, 0.99	.;D;D;D
Vest4		0.21
MutPred		0.73		Gain of ubiquitination at K89 (P = 0.0357);Gain of ubiquitination at K89 (P = 0.0357);Gain of ubiquitination at K89 (P = 0.0357);Gain of ubiquitination at K89 (P = 0.0357);
MVP		0.16
MPC		1.1
ClinPred		0.95	D
GERP RS		0.55
Varity_R		0.74
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000083
dbscSNV1_RF	Benign	0.058
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

LitVar

Other links and lift over

dbSNP: rs369119006; hg19: chr9-138439092;