rs8192646

Variant names:

• chr6-132617703-C-T
• rs8192646
• NM_001033080.1:c.503G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001033080.1(TAAR2):​c.503G>A​(p.Trp168*) 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
• Publications: 16 publications found

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]

ENSG00000290584 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033080.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAAR2	NM_001033080.1	MANE Select	c.503G>A	p.Trp168*	stop_gained	Exon 2 of 2	NP_001028252.1
	TAAR2	NM_014626.3		c.368G>A	p.Trp123*	stop_gained	Exon 1 of 1	NP_055441.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAAR2	ENST00000367931.1	TSL:1 MANE Select	c.503G>A	p.Trp168*	stop_gained	Exon 2 of 2	ENSP00000356908.1
	TAAR2	ENST00000275191.2	TSL:6	c.368G>A	p.Trp123*	stop_gained	Exon 1 of 1	ENSP00000275191.2
	ENSG00000290584	ENST00000466706.2	TSL:6	n.171-958G>A		intron	N/A

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

GnomAD2 exomes AF: 0.0364 AC: 9079 AN: 249504 AF XY: 0.0378

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 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

African (AFR) AF: 0.0135 AC: 452 AN: 33480

American (AMR) AF: 0.00816 AC: 365 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0169 AC: 442 AN: 26132

East Asian (EAS) AF: 0.140 AC: 5545 AN: 39634

South Asian (SAS) AF: 0.0583 AC: 5030 AN: 86258

European-Finnish (FIN) AF: 0.0149 AC: 797 AN: 53328

Middle Eastern (MID) AF: 0.0291 AC: 168 AN: 5766

European-Non Finnish (NFE) AF: 0.0220 AC: 24516 AN: 1111958

Other (OTH) AF: 0.0357 AC: 2158 AN: 60386

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

African (AFR) AF: 0.0127 AC: 527 AN: 41528

American (AMR) AF: 0.0154 AC: 236 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3472

East Asian (EAS) AF: 0.186 AC: 963 AN: 5180

South Asian (SAS) AF: 0.0679 AC: 327 AN: 4818

European-Finnish (FIN) AF: 0.0140 AC: 148 AN: 10584

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0248 AC: 1683 AN: 67996

Other (OTH) AF: 0.0251 AC: 53 AN: 2114

Alfa AF: 0.0253 Hom.: 360

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 v4.9

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
PhyloP100		6.1
Vest4		0.24
GERP RS		6.0
PromoterAI		-0.0024	Neutral
Mutation Taster		=171/29	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8192646; hg19: chr6-132938842; COSMIC: COSV51579147;