Genetic Variant TACR2:p.Arg323His (chr10-69405055-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001057.3(TACR2):c.968G>A(p.Arg323His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,613,734 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R323C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 32 hom. )

Consequence

TACR2
NM_001057.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.589

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076259673).

BP6

Variant 10-69405055-C-T is Benign according to our data. Variant chr10-69405055-C-T is described in ClinVar as [Benign]. Clinvar id is 714484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR2	NM_001057.3 link	c.968G>A	p.Arg323His	missense_variant	Exon 5 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.968G>A	p.Arg323His	missense_variant	Exon 5 of 5	1	NM_001057.3	ENSP00000362403.4		P21452
TACR2	ENST00000373307.5 link	c.332G>A	p.Arg111His	missense_variant	Exon 3 of 3	2		ENSP00000362404.1		A6NEW7

Frequencies

GnomAD3 genomes

AF:

0.00312

AC:

475

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00613

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00322

AC:

799

AN:

248354

Hom.:

AF XY:

0.00384

AC XY:

517

AN XY:

134468

show subpopulations

Gnomad AFR exome

AF:

0.00579

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0131

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00190

Gnomad OTH exome

AF:

0.00263

GnomAD4 exome

AF:

0.00202

AC:

2953

AN:

1461494

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

1757

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.00616

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0132

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.00239

GnomAD4 genome

AF:

0.00312

AC:

475

AN:

152240

Hom.:

Cov.:

AF XY:

0.00359

AC XY:

267

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00614

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0112

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00166

Hom.:

Bravo

AF:

0.00315

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00348

AC:

423

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.00262

EpiControl

AF:

0.00285

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 18, 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

0.072

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.067

FATHMM_MKL

Benign

0.28

LIST_S2

Uncertain

0.89

D;D;D

MetaRNN

Benign

0.0076

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

.;.;L

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-3.2

D;.;N

REVEL

Benign

0.15

Sift

Uncertain

0.0070

D;.;D

Sift4G

Benign

0.24

T;T;T

Polyphen

0.11

.;.;B

Vest4

0.41

MVP

0.63

MPC

0.34

ClinPred

0.018

GERP RS

3.8

Varity_R

0.11

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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