2-11662020-C-T

Variant names:

• chr2-11662020-C-T
• rs34764121
• NM_012344.4:c.845G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012344.4(NTSR2):​c.845G>A​(p.Arg282Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,612,804 control chromosomes in the GnomAD database, including 232 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (136 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (96 hom.)
• Consequence: NTSR2 NM_012344.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.65
• Publications: 5 publications found

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029715598).
• BP6: Variant 2-11662020-C-T is Benign according to our data. Variant chr2-11662020-C-T is described in ClinVar as Benign. ClinVar VariationId is 782401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

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.845G>A	p.Arg282Lys	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.845G>A	p.Arg282Lys	missense	Exon 2 of 4	ENSP00000303686.5	O95665
	NTSR2	ENST00000950908.1		c.840+5G>A		splice_region intron	N/A	ENSP00000620967.1

Frequencies

GnomAD3 genomes AF: 0.0226 AC: 3441 AN: 152206 Hom.: 136 Cov.: 33

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.00638 AC: 1595 AN: 250040 AF XY: 0.00469

Gnomad AFR exome AF: 0.0797

Gnomad AMR exome AF: 0.00453

Gnomad ASJ exome AF: 0.00828

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00412

GnomAD4 exome AF: 0.00242 AC: 3528 AN: 1460480 Hom.: 96 Cov.: 31 AF XY: 0.00213 AC XY: 1547 AN XY: 726464

African (AFR) AF: 0.0737 AC: 2465 AN: 33426

American (AMR) AF: 0.00561 AC: 250 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00755 AC: 197 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53162

Middle Eastern (MID) AF: 0.00382 AC: 22 AN: 5762

European-Non Finnish (NFE) AF: 0.000209 AC: 232 AN: 1111448

Other (OTH) AF: 0.00573 AC: 346 AN: 60352

GnomAD4 genome AF: 0.0226 AC: 3446 AN: 152324 Hom.: 136 Cov.: 33 AF XY: 0.0219 AC XY: 1633 AN XY: 74488

African (AFR) AF: 0.0764 AC: 3174 AN: 41568

American (AMR) AF: 0.0118 AC: 180 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00951 AC: 33 AN: 3470

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

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68036

Other (OTH) AF: 0.0151 AC: 32 AN: 2114

Alfa AF: 0.00930 Hom.: 101

Bravo AF: 0.0271

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0715 AC: 315

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.00790 AC: 959

Asia WGS AF: 0.00664 AC: 24 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000238

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.25
Sift	Benign	0.81	T
Sift4G	Benign	0.55	T
Polyphen		0.98	D
Vest4		0.34
MVP		0.84
MPC		0.63
ClinPred		0.046	T
GERP RS		1.2
Varity_R		0.10
gMVP		0.27
Mutation Taster		=90/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs34764121; hg19: chr2-11802146;