Genetic Variant NTSR2:p.Arg294Leu (chr2-11661984-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012344.4(NTSR2):c.881G>T(p.Arg294Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R294H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NTSR2
NM_012344.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.456

Publications

0 publications found

Variant links:

Genes affected

NTSR2 (HGNC:8040): (neurotensin receptor 2) The protein encoded by this gene belongs to the G protein-coupled receptor family that activate a phosphatidylinositol-calcium second messenger system. Binding and pharmacological studies demonstrate that this receptor binds neurotensin as well as several other ligands already described for neurotensin NT1 receptor. However, unlike NT1 receptor, this gene recognizes, with high affinity, levocabastine, a histamine H1 receptor antagonist previously shown to compete with neurotensin for low-affinity binding sites in brain. These activities suggest that this receptor may be of physiological importance and that a natural agonist for the receptor may exist. [provided by RefSeq, Jul 2008]

NTSR2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16165623).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012344.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTSR2	NM_012344.4	MANE Select	c.881G>T	p.Arg294Leu	missense	Exon 2 of 4	NP_036476.2	O95665

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTSR2	ENST00000306928.6	TSL:1 MANE Select	c.881G>T	p.Arg294Leu	missense	Exon 2 of 4	ENSP00000303686.5	O95665
	NTSR2	ENST00000950908.1		c.840+41G>T		intron	N/A	ENSP00000620967.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1451692

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721584

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33158

American (AMR)

AF:

0.00

AC:

AN:

43542

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25508

East Asian (EAS)

AF:

0.00

AC:

AN:

39302

South Asian (SAS)

AF:

0.00

AC:

AN:

84612

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52884

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1107034

Other (OTH)

AF:

0.00

AC:

AN:

59932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.41

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.67

M_CAP

Benign

0.0062

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

-0.46

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.061

Sift

Benign

0.047

Sift4G

Benign

0.19

Polyphen

0.0020

Vest4

0.20

MutPred

0.44

Loss of MoRF binding (P = 0.0419)

MVP

0.44

MPC

0.18

ClinPred

0.63

GERP RS

-5.6

Varity_R

0.22

gMVP

0.34

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over