rs8192646

Positions:

• chr6-132617703-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001033080.1(TAAR2):​c.503G>A​(p.Trp168Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0269 in 1,613,828 control chromosomes in the GnomAD database, including 1,203 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.026 (127 hom., cov: 32)
  • Exomes 𝑓: 0.027 (1076 hom.)
• Consequence: TAAR2 NM_001033080.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.06

Genes affected

TAAR2 (HGNC:4514): (trace amine associated receptor 2) Predicted to enable trace-amine receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAAR2	NM_001033080.1	c.503G>A	p.Trp168Ter	stop_gained	2/2	ENST00000367931.1
TAAR2	NM_014626.3	c.368G>A	p.Trp123Ter	stop_gained	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAAR2	ENST00000367931.1	c.503G>A	p.Trp168Ter	stop_gained	2/2	1	NM_001033080.1	A2
TAAR2	ENST00000275191.2	c.368G>A	p.Trp123Ter	stop_gained	1/1			P4

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3990 AN: 152058 Hom.: 126 Cov.: 32

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0676

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0220

GnomAD3 exomes AF: 0.0364 AC: 9079 AN: 249504 Hom.: 506 AF XY: 0.0378 AC XY: 5107 AN XY: 134982

Gnomad AFR exome AF: 0.0124

Gnomad AMR exome AF: 0.00808

Gnomad ASJ exome AF: 0.0147

Gnomad EAS exome AF: 0.197

Gnomad SAS exome AF: 0.0571

Gnomad FIN exome AF: 0.0158

Gnomad NFE exome AF: 0.0230

Gnomad OTH exome AF: 0.0297

GnomAD4 exome AF: 0.0270 AC: 39473 AN: 1461652 Hom.: 1076 Cov.: 31 AF XY: 0.0282 AC XY: 20478 AN XY: 727128

Gnomad4 AFR exome AF: 0.0135

Gnomad4 AMR exome AF: 0.00816

Gnomad4 ASJ exome AF: 0.0169

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.0583

Gnomad4 FIN exome AF: 0.0149

Gnomad4 NFE exome AF: 0.0220

Gnomad4 OTH exome AF: 0.0357

GnomAD4 genome AF: 0.0262 AC: 3990 AN: 152176 Hom.: 127 Cov.: 32 AF XY: 0.0267 AC XY: 1985 AN XY: 74376

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.0679

Gnomad4 FIN AF: 0.0140

Gnomad4 NFE AF: 0.0248

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0258 Hom.: 211

Bravo AF: 0.0247

TwinsUK AF: 0.0248 AC: 92

ALSPAC AF: 0.0179 AC: 69

ESP6500AA AF: 0.0141 AC: 62

ESP6500EA AF: 0.0219 AC: 188

ExAC AF: 0.0362 AC: 4398

Asia WGS AF: 0.119 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Pathogenic	0.66
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Pathogenic	0.77
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.97	D
MutationTaster	Benign	1.4e-22	P;P;P
Vest4		0.24
GERP RS		6.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs8192646; hg19: chr6-132938842; COSMIC: COSV51579147;