chr1-18840056-A-G

Variant names:

• chr1-18840056-A-G
• rs368232043
• NM_152232.6:c.2063T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_152232.6(TAS1R2):​c.2063T>C​(p.Leu688Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: TAS1R2 NM_152232.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.43
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.909

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS1R2	NM_152232.6	c.2063T>C	p.Leu688Pro	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	c.2063T>C	p.Leu688Pro	missense_variant	Exon 6 of 6	2	NM_152232.6	ENSP00000364520.3

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152198 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251490 AF XY: 0.00

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461892 Hom.: 0 Cov.: 38 AF XY: 0.00000550 AC XY: 4 AN XY: 727246

African (AFR) AF: 0.000358 AC: 12 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152316 Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4 AN XY: 74484

African (AFR) AF: 0.000216 AC: 9 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000219 Hom.: 0

Bravo AF: 0.0000604

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2063T>C (p.L688P) alteration is located in exon 6 (coding exon 6) of the TAS1R2 gene. This alteration results from a T to C substitution at nucleotide position 2063, causing the leucine (L) at amino acid position 688 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.049
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.4
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.6	D
REVEL	Pathogenic	0.69
Sift	Benign	0.039	D
Sift4G	Benign	0.064	T
Polyphen		1.0	D
Vest4		0.69
MVP		0.94
MPC		0.73
ClinPred		0.84	D
GERP RS		5.0
Varity_R		0.85
gMVP		0.76
Mutation Taster		=62/38	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: rs368232043; hg19: chr1-19166550;