Genetic Variant NM_152232.6:c.2513G>A (chr1-18839606-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152232.6(TAS1R2):c.2513G>A(p.Arg838Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,614,096 control chromosomes in the GnomAD database, including 1,041 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.050 ( 525 hom., cov: 33)

Exomes 𝑓: 0.012 ( 516 hom. )

Consequence

TAS1R2
NM_152232.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.161

Publications

11 publications found

Variant links:

Genes affected

TAS1R2 (HGNC:14905): (taste 1 receptor member 2) Contributes to sweet taste receptor activity. Involved in detection of chemical stimulus involved in sensory perception of sweet taste and positive regulation of cytokinesis. Part of sweet taste receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

TAS1R2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014762282).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS1R2	NM_152232.6 link	c.2513G>A	p.Arg838Lys	missense_variant	Exon 6 of 6	ENST00000375371.4	NP_689418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS1R2	ENST00000375371.4 link	c.2513G>A	p.Arg838Lys	missense_variant	Exon 6 of 6	2	NM_152232.6	ENSP00000364520.3

Frequencies

GnomAD3 genomes

AF:

0.0498

AC:

7581

AN:

152170

Hom.:

523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0324

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.00593

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.00804

Gnomad OTH

AF:

0.0497

GnomAD2 exomes

AF:

0.0204

AC:

5127

AN:

250712

AF XY:

0.0181

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.0123

Gnomad ASJ exome

AF:

0.0253

Gnomad EAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.00669

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.0160

GnomAD4 exome

AF:

0.0123

AC:

18024

AN:

1461808

Hom.:

516

Cov.:

AF XY:

0.0120

AC XY:

8757

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.155

AC:

5173

AN:

33478

American (AMR)

AF:

0.0143

AC:

640

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0259

AC:

677

AN:

26132

East Asian (EAS)

AF:

0.000403

AC:

AN:

39700

South Asian (SAS)

AF:

0.0151

AC:

1299

AN:

86226

European-Finnish (FIN)

AF:

0.00676

AC:

361

AN:

53414

Middle Eastern (MID)

AF:

0.0198

AC:

114

AN:

5768

European-Non Finnish (NFE)

AF:

0.00773

AC:

8601

AN:

1111988

Other (OTH)

AF:

0.0189

AC:

1143

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1012

2023

3035

4046

5058

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

382

764

1146

1528

1910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0498

AC:

7588

AN:

152288

Hom.:

525

Cov.:

AF XY:

0.0476

AC XY:

3547

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.150

AC:

6216

AN:

41538

American (AMR)

AF:

0.0323

AC:

495

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0239

AC:

AN:

3472

East Asian (EAS)

AF:

0.000965

AC:

AN:

5182

South Asian (SAS)

AF:

0.0139

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00593

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00806

AC:

548

AN:

68022

Other (OTH)

AF:

0.0501

AC:

106

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

334

668

1001

1335

1669

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0193

Hom.:

314

Bravo

AF:

0.0567

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.139

AC:

613

ESP6500EA

AF:

0.00698

AC:

ExAC

AF:

0.0238

AC:

2894

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.00834

EpiControl

AF:

0.00961

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.046

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.021

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0088

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

-0.16

PrimateAI

Benign

0.29

PROVEAN

Benign

0.81

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.010

ClinPred

0.0011

GERP RS

-5.4

Varity_R

0.032

gMVP

0.25

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over