1-248650176-C-A

Variant names:

• chr1-248650176-C-A
• rs772347670
• NM_001001824.2:c.709G>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001001824.2(OR2T27):​c.709G>T​(p.Ala237Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,564,902 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000035 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000019 (3 hom.)
• Consequence: OR2T27 NM_001001824.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29

Genes affected

OR2T27 (HGNC:31252): (olfactory receptor family 2 subfamily T member 27) 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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.41777077).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2T27	NM_001001824.2	c.709G>T	p.Ala237Ser	missense_variant	Exon 2 of 2	ENST00000460972.4	NP_001001824.1
OR2T27	NM_001386060.1	c.709G>T	p.Ala237Ser	missense_variant	Exon 3 of 3		NP_001372989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2T27	ENST00000460972.4	c.709G>T	p.Ala237Ser	missense_variant	Exon 2 of 2	6	NM_001001824.2	ENSP00000493412.1
OR2T27	ENST00000641652.1	c.709G>T	p.Ala237Ser	missense_variant	Exon 3 of 3			ENSP00000493434.1

Frequencies

GnomAD3 genomes AF: 0.0000353 AC: 5 AN: 141776 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000705

Gnomad ASJ AF: 0.000896

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000514

GnomAD3 exomes AF: 0.0000418 AC: 10 AN: 239238 Hom.: 0 AF XY: 0.0000309 AC XY: 4 AN XY: 129246

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000606

Gnomad EAS exome AF: 0.000116

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000926

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.0000190 AC: 27 AN: 1423012 Hom.: 3 Cov.: 33 AF XY: 0.0000127 AC XY: 9 AN XY: 708102

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000232

Gnomad4 ASJ exome AF: 0.000388

Gnomad4 EAS exome AF: 0.0000782

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000831

Gnomad4 OTH exome AF: 0.0000677

GnomAD4 genome AF: 0.0000352 AC: 5 AN: 141890 Hom.: 0 Cov.: 26 AF XY: 0.0000726 AC XY: 5 AN XY: 68834

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000704

Gnomad4 ASJ AF: 0.000896

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000509

Alfa AF: 0.0000435 Hom.: 0

ExAC AF: 0.0000336 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.709G>T (p.A237S) alteration is located in exon 1 (coding exon 1) of the OR2T27 gene. This alteration results from a G to T substitution at nucleotide position 709, causing the alanine (A) at amino acid position 237 to be replaced by a serine (S). 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	0.17
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0086	T;T;T
Eigen	Uncertain	0.24
Eigen_PC	Benign	-0.0017
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	.;.;T
M_CAP	Benign	0.00089	T
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.8	.;.;D
REVEL	Benign	0.12
Sift	Uncertain	0.0040	.;.;D
Sift4G	Uncertain	0.043	.;.;D
Polyphen		1.0	D;D;D
Vest4		0.43
MutPred		0.59		Gain of disorder (P = 0.0288);Gain of disorder (P = 0.0288);Gain of disorder (P = 0.0288);
MVP		0.62
MPC		1.3
ClinPred		0.52	D
GERP RS		2.5
Varity_R		0.33
gMVP		0.043

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

Other links and lift over

dbSNP: rs772347670; hg19: chr1-248813477;