dbSNP rs142415572: TACR2:p.Thr251Ala (chr10-69407271-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001057.3(TACR2):c.751A>G(p.Thr251Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00323 in 1,611,244 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 80 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 69 hom. )

Consequence

TACR2
NM_001057.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.26

Variant links:

Genes affected

TACR2 (HGNC:11527): (tachykinin receptor 2) This gene belongs to a family of genes that function as receptors for tachykinins. Receptor affinities are specified by variations in the 5'-end of the sequence. The receptors belonging to this family are characterized by interactions with G proteins and 7 hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin neuropeptide substance K, also referred to as neurokinin A. [provided by RefSeq, Jul 2008]

TACR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048061013).

BP6

Variant 10-69407271-T-C is Benign according to our data. Variant chr10-69407271-T-C is described in ClinVar as [Benign]. Clinvar id is 779115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR2	NM_001057.3 link	c.751A>G	p.Thr251Ala	missense_variant	Exon 4 of 5	ENST00000373306.5	NP_001048.2	P21452

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR2	ENST00000373306.5 link	c.751A>G	p.Thr251Ala	missense_variant	Exon 4 of 5	1	NM_001057.3	ENSP00000362403.4		P21452
TACR2	ENST00000373307.5 link	c.115A>G	p.Thr39Ala	missense_variant	Exon 2 of 3	2		ENSP00000362404.1		A6NEW7

Frequencies

GnomAD3 genomes

AF:

0.0175

AC:

2655

AN:

151950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0609

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00701

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00468

AC:

1159

AN:

247858

Hom.:

AF XY:

0.00349

AC XY:

468

AN XY:

134022

show subpopulations

Gnomad AFR exome

AF:

0.0642

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000205

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00174

AC:

2544

AN:

1459176

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

1084

AN XY:

725872

show subpopulations

Gnomad4 AFR exome

AF:

0.0630

Gnomad4 AMR exome

AF:

0.00285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000585

Gnomad4 OTH exome

AF:

0.00382

GnomAD4 genome

AF:

0.0175

AC:

2659

AN:

152068

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1246

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0608

Gnomad4 AMR

AF:

0.00700

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00312

Hom.:

Bravo

AF:

0.0203

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0597

AC:

263

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00582

AC:

707

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

.;.;T

Eigen

Benign

-0.049

Eigen_PC

Benign

0.070

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.77

T;T;T

MetaRNN

Benign

0.0048

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

.;.;M

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.94

N;.;N

REVEL

Benign

0.14

Sift

Benign

0.084

T;.;T

Sift4G

Uncertain

0.046

D;T;T

Polyphen

0.0030

.;.;B

Vest4

0.42

MVP

0.64

MPC

0.27

ClinPred

0.039

GERP RS

3.6

Varity_R

0.10

gMVP

0.83

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over