chr2-11662108-G-T

Variant names:

• chr2-11662108-G-T
• rs148798482
• NM_012344.4:c.757C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_012344.4(NTSR2):​c.757C>A​(p.Arg253Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000487 in 1,613,078 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R253C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00035 (1 hom.)
• Consequence: NTSR2 NM_012344.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.67

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.007001847).
• BP6: Variant 2-11662108-G-T is Benign according to our data. Variant chr2-11662108-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 738625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTSR2	NM_012344.4	c.757C>A	p.Arg253Ser	missense_variant	Exon 2 of 4	ENST00000306928.6	NP_036476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTSR2	ENST00000306928.6	c.757C>A	p.Arg253Ser	missense_variant	Exon 2 of 4	1	NM_012344.4	ENSP00000303686.5

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 270 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00569

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

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: 0.000118

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000573 AC: 143 AN: 249434 AF XY: 0.000518

Gnomad AFR exome AF: 0.00566

Gnomad AMR exome AF: 0.000645

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000352 AC: 514 AN: 1460744 Hom.: 1 Cov.: 31 AF XY: 0.000332 AC XY: 241 AN XY: 726656

Gnomad4 AFR exome AF: 0.00538 AC: 180 AN: 33440

Gnomad4 AMR exome AF: 0.000650 AC: 29 AN: 44644

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26116

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39662

Gnomad4 SAS exome AF: 0.0000232 AC: 2 AN: 86118

Gnomad4 FIN exome AF: 0.0000189 AC: 1 AN: 52956

Gnomad4 NFE exome AF: 0.000233 AC: 259 AN: 1111688

Gnomad4 Remaining exome AF: 0.000646 AC: 39 AN: 60358

GnomAD4 genome AF: 0.00178 AC: 271 AN: 152334 Hom.: 0 Cov.: 33 AF XY: 0.00166 AC XY: 124 AN XY: 74498

Gnomad4 AFR AF: 0.00570 AC: 0.00569986 AN: 0.00569986

Gnomad4 AMR AF: 0.00157 AC: 0.00156781 AN: 0.00156781

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000118 AC: 0.000117612 AN: 0.000117612

Gnomad4 OTH AF: 0.000946 AC: 0.000946074 AN: 0.000946074

Alfa AF: 0.000505 Hom.: 0

Bravo AF: 0.00214

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00499 AC: 22

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000667 AC: 81

EpiCase AF: 0.000109

EpiControl AF: 0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.0070	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.11
Sift	Benign	0.087	T
Sift4G	Benign	0.17	T
Polyphen		0.065	B
Vest4		0.24
MVP		0.66
MPC		0.35
ClinPred		0.016	T
GERP RS		2.5
Varity_R		0.16
gMVP		0.28
Mutation Taster		=93/7	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

Publications

LitVar

Other links and lift over

dbSNP: rs148798482; hg19: chr2-11802234;