chr11-124319705-C-T

Variant names:

• chr11-124319705-C-T
• rs2137799828
• NM_001002918.1:c.493G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001002918.1(OR8D2):​c.493G>A​(p.Val165Met) 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V165A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR8D2 NM_001002918.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.492
• Publications: 0 publications found

Genes affected

OR8D2 (HGNC:8482): (olfactory receptor family 8 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

LOC112268069 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039719343).
• BP6: Variant 11-124319705-C-T is Benign according to our data. Variant chr11-124319705-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2394586.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002918.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR8D2	NM_001002918.1	MANE Select	c.493G>A	p.Val165Met	missense	Exon 1 of 1	NP_001002918.1	A0A126GVG3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR8D2	ENST00000624618.2	TSL:6 MANE Select	c.493G>A	p.Val165Met	missense	Exon 1 of 1	ENSP00000485661.1	Q9GZM6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.79
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.060	N
PhyloP100		-0.49
PrimateAI	Benign	0.21	T
Polyphen		0.0020	B
MutPred		0.35		Gain of loop (P = 0.1069)
ClinPred		0.078	T
GERP RS		-2.5
PromoterAI		0.013	Neutral
Varity_R		0.024
gMVP		0.048
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2137799828; hg19: chr11-124189601; COSMIC: COSV62488108; COSMIC: COSV62488108;