14-19713321-A-C

Position:

• chr14-19713321-A-C

Variant summary

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

The NM_001197287.2(OR11H2):​c.563T>G​(p.Leu188Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0013 in 151,314 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00070 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR11H2 NM_001197287.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.26

Genes affected

OR11H2 (HGNC:14716): (olfactory receptor family 11 subfamily H 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR11H2	NM_001197287.2	c.563T>G	p.Leu188Arg	missense_variant	1/1	ENST00000556246.3	NP_001184216.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR11H2	ENST00000556246.3	c.563T>G	p.Leu188Arg	missense_variant	1/1	6	NM_001197287.2	ENSP00000485150.2

Frequencies

GnomAD3 genomes AF: 0.00130 AC: 197 AN: 151198 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000462

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000989

Gnomad ASJ AF: 0.000868

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00224

Gnomad OTH AF: 0.000481

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000704 AC: 1025 AN: 1455824 Hom.: 2 Cov.: 33 AF XY: 0.000704 AC XY: 510 AN XY: 724210

Gnomad4 AFR exome AF: 0.000390

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.000651

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000826

Gnomad4 NFE exome AF: 0.000807

Gnomad4 OTH exome AF: 0.000666

GnomAD4 genome AF: 0.00130 AC: 197 AN: 151314 Hom.: 0 Cov.: 27 AF XY: 0.00114 AC XY: 84 AN XY: 74000

Gnomad4 AFR AF: 0.000461

Gnomad4 AMR AF: 0.000987

Gnomad4 ASJ AF: 0.000868

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000660

Gnomad4 NFE AF: 0.00224

Gnomad4 OTH AF: 0.000476

Alfa AF: 0.00178 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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

Oct 03, 2022

The c.596T>G (p.L199R) alteration is located in exon 2 (coding exon 1) of the OR11H2 gene. This alteration results from a T to G substitution at nucleotide position 596, causing the leucine (L) at amino acid position 199 to be replaced by an arginine (R). 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	0.28
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	24
DANN	Benign	0.45
DEOGEN2	Benign	0.025	T;.
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.70	T;T
MetaRNN	Uncertain	0.60	D;D
MutationAssessor	Pathogenic	4.3	H;.
PrimateAI	Benign	0.37	T
MVP		0.46
GERP RS		1.3
Varity_R		0.15
gMVP		0.086

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs777093773; hg19: chr14-20181480;