dbSNP rs369973889: OR7D2:p.Pro25Gln (chr19-9185855-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_175883.4(OR7D2):c.74C>A(p.Pro25Gln) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P25L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR7D2
NM_175883.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.728

Variant links:

Genes affected

OR7D2 (HGNC:8378): (olfactory receptor family 7 subfamily D 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]

OR7D2 links:

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ACMG classification

Classification made for transcript

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=0.17967686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR7D2	NM_175883.4 link	c.74C>A	p.Pro25Gln	missense_variant	Exon 3 of 3	ENST00000641288.2	NP_787079.1	Q96RA2
OR7D2	NM_001386112.1 link	c.74C>A	p.Pro25Gln	missense_variant	Exon 2 of 2		NP_001373041.1
OR7D2	XM_047438317.1 link	c.74C>A	p.Pro25Gln	missense_variant	Exon 2 of 2		XP_047294273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR7D2	ENST00000641288.2 link	c.74C>A	p.Pro25Gln	missense_variant	Exon 3 of 3		NM_175883.4	ENSP00000493200.1	Q96RA2
OR7D2	ENST00000344248.4 link	c.74C>A	p.Pro25Gln	missense_variant	Exon 1 of 1	6		ENSP00000345563.2	Q96RA2
OR7D2	ENST00000642043.1 link	c.74C>A	p.Pro25Gln	missense_variant	Exon 2 of 2			ENSP00000492939.1	Q96RA2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460606

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726594

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

T;T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.40

.;.;T

M_CAP

Benign

0.0010

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.2

L;L;L

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-4.2

.;.;D

REVEL

Benign

0.060

Sift

Uncertain

0.0030

.;.;D

Sift4G

Uncertain

0.038

.;.;D

Polyphen

1.0

D;D;D

Vest4

0.23

MutPred

0.34

Loss of catalytic residue at P25 (P = 0.0728);Loss of catalytic residue at P25 (P = 0.0728);Loss of catalytic residue at P25 (P = 0.0728);

MVP

0.55

MPC

0.17

ClinPred

0.89

GERP RS

2.2

Varity_R

0.10

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over