Variant chr19-9186527-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_175883.4(OR7D2):c.746C>G(p.Ser249Cys) 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. 15/20 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)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR7D2
NM_175883.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.964

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=0.13233712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR7D2	NM_175883.4 linkuse as main transcript	c.746C>G	p.Ser249Cys	missense_variant	3/3	ENST00000641288.2
OR7D2	NM_001386112.1 linkuse as main transcript	c.746C>G	p.Ser249Cys	missense_variant	2/2
OR7D2	XM_047438317.1 linkuse as main transcript	c.746C>G	p.Ser249Cys	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Appris
OR7D2	ENST00000641288.2 linkuse as main transcript	c.746C>G	p.Ser249Cys	missense_variant	3/3	NM_175883.4	P1
OR7D2	ENST00000344248.4 linkuse as main transcript	c.746C>G	p.Ser249Cys	missense_variant	1/1		P1
OR7D2	ENST00000642043.1 linkuse as main transcript	c.746C>G	p.Ser249Cys	missense_variant	2/2		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000208

AC:

AN:

1439478

Hom.:

Cov.:

AF XY:

0.00000418

AC XY:

AN XY:

716932

show subpopulations

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:

0.00000273

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.746C>G (p.S249C) alteration is located in exon 1 (coding exon 1) of the OR7D2 gene. This alteration results from a C to G substitution at nucleotide position 746, causing the serine (S) at amino acid position 249 to be replaced by a cysteine (C). 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

0.059

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.12

T;T;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.088

.;.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

-2.3

.;.;N

REVEL

Benign

0.050

Sift

Benign

0.11

.;.;T

Sift4G

Benign

0.19

.;.;T

Polyphen

0.19

B;B;B

Vest4

0.14

MutPred

0.59

Gain of catalytic residue at L250 (P = 0.0181);Gain of catalytic residue at L250 (P = 0.0181);Gain of catalytic residue at L250 (P = 0.0181);

MVP

0.29

MPC

0.14

ClinPred

0.37

GERP RS

-0.30

Varity_R

0.17

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over