rs9988418

Positions:

• chr1-18839606-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.050 (525 hom., cov: 33)
  • Exomes 𝑓: 0.012 (516 hom.)
• Consequence: TAS1R2 NM_152232.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TAS1R2	NM_152232.6	c.2513G>A	p.Arg838Lys	missense_variant	6/6	ENST00000375371.4	NP_689418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R2	ENST00000375371.4	c.2513G>A	p.Arg838Lys	missense_variant	6/6	2	NM_152232.6	ENSP00000364520.3

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7581 AN: 152170 Hom.: 523 Cov.: 33

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

GnomAD3 exomes AF: 0.0204 AC: 5127 AN: 250712 Hom.: 227 AF XY: 0.0181 AC XY: 2448 AN XY: 135520

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 SAS exome AF: 0.0142

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.: 51 AF XY: 0.0120 AC XY: 8757 AN XY: 727184

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.0143

Gnomad4 ASJ exome AF: 0.0259

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.0151

Gnomad4 FIN exome AF: 0.00676

Gnomad4 NFE exome AF: 0.00773

Gnomad4 OTH exome AF: 0.0189

GnomAD4 genome AF: 0.0498 AC: 7588 AN: 152288 Hom.: 525 Cov.: 33 AF XY: 0.0476 AC XY: 3547 AN XY: 74470

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0323

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.00593

Gnomad4 NFE AF: 0.00806

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0150 Hom.: 136

Bravo AF: 0.0567

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.00675 AC: 26

ESP6500AA AF: 0.139 AC: 613

ESP6500EA AF: 0.00698 AC: 60

ExAC AF: 0.0238 AC: 2894

Asia WGS AF: 0.0180 AC: 61 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	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.046
DANN	Benign	0.50
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0088	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.81	N
REVEL	Benign	0.18
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.010
MPC		0.12
ClinPred		0.0011	T
GERP RS		-5.4
Varity_R		0.032
gMVP		0.25

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

Other links and lift over

dbSNP: rs9988418; hg19: chr1-19166100; COSMIC: COSV104684318;