12-55452275-T-G

Position:

• chr12-55452275-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_054105.2(OR6C2):​c.62T>G​(p.Leu21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,570 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OR6C2 NM_054105.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.700

Genes affected

OR6C2 (HGNC:15436): (olfactory receptor family 6 subfamily C 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]

ENSG00000258763 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR6C2	NM_054105.2	c.62T>G	p.Leu21Arg	missense_variant	2/2	ENST00000641202.1	NP_473446.1
LOC124902940	XR_007063324.1	n.88+211A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR6C2	ENST00000641202.1	c.62T>G	p.Leu21Arg	missense_variant	2/2		NM_054105.2	ENSP00000493222.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460570 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726526

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jul 13, 2022

The c.62T>G (p.L21R) alteration is located in exon 1 (coding exon 1) of the OR6C2 gene. This alteration results from a T to G substitution at nucleotide position 62, causing the leucine (L) at amino acid position 21 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	0.18
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.087	T;T;T
Eigen	Benign	0.014
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.86	.;.;D
M_CAP	Benign	0.0018	T
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M;M;M
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-4.8	.;.;D
REVEL	Benign	0.13
Sift	Pathogenic	0.0	.;.;D
Sift4G	Uncertain	0.0090	.;.;D
Polyphen		0.95	P;P;P
Vest4		0.70
MutPred		0.73		Loss of stability (P = 0.1621);Loss of stability (P = 0.1621);Loss of stability (P = 0.1621);
MVP		0.27
MPC		0.0042
ClinPred		0.73	D
GERP RS		4.1
Varity_R		0.59
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-55846059;