rs1296881171

Variant names:

• chr6-132617347-A-G
• rs1296881171
• NM_001033080.1:c.859T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001033080.1(TAAR2):​c.859T>C​(p.Phe287Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,346 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: 6.8e-7 (0 hom.)
• Consequence: TAAR2 NM_001033080.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.03
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAAR2	NM_001033080.1	MANE Select	c.859T>C	p.Phe287Leu	missense	Exon 2 of 2	NP_001028252.1	Q9P1P5-1
	TAAR2	NM_014626.3		c.724T>C	p.Phe242Leu	missense	Exon 1 of 1	NP_055441.2	Q9P1P5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAAR2	ENST00000367931.1	TSL:1 MANE Select	c.859T>C	p.Phe287Leu	missense	Exon 2 of 2	ENSP00000356908.1	Q9P1P5-1
	TAAR2	ENST00000275191.2	TSL:6	c.724T>C	p.Phe242Leu	missense	Exon 1 of 1	ENSP00000275191.2	Q9P1P5-2
	ENSG00000290584	ENST00000466706.2	TSL:6	n.171-602T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250208 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000551

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461346 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726962

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39554

South Asian (SAS) AF: 0.00 AC: 0 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111826

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T
Eigen	Benign	0.079
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0068	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.17
Sift	Uncertain	0.025	D
Sift4G	Benign	0.20	T
Polyphen		0.73	P
Vest4		0.53
MutPred		0.65		Gain of catalytic residue at F287 (P = 0.0191)
MVP		0.44
MPC		0.022
ClinPred		0.92	D
GERP RS		6.1
Varity_R		0.38
gMVP		0.30
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs1296881171; hg19: chr6-132938486;