2-11658548-C-T

Variant names:

• chr2-11658548-C-T
• rs138784927
• NM_012344.4:c.1164G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_012344.4(NTSR2):​c.1164G>A​(p.Pro388Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000994 in 1,614,120 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00097 (6 hom.)
• Consequence: NTSR2 NM_012344.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.69
• Publications: 1 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]

ENSG00000303313 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 2-11658548-C-T is Benign according to our data. Variant chr2-11658548-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2650686.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.69 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

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.1164G>A	p.Pro388Pro	synonymous	Exon 4 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.1164G>A	p.Pro388Pro	synonymous	Exon 4 of 4	ENSP00000303686.5	O95665
	NTSR2	ENST00000950908.1		c.1212G>A	p.Pro404Pro	synonymous	Exon 5 of 5	ENSP00000620967.1
	ENSG00000303313	ENST00000793551.1		n.374-39C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 181 AN: 152130 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00232

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00106 AC: 267 AN: 251382 AF XY: 0.00108

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00143

Gnomad NFE exome AF: 0.00200

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000974 AC: 1424 AN: 1461872 Hom.: 6 Cov.: 31 AF XY: 0.00104 AC XY: 756 AN XY: 727236

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26134

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00170 AC: 91 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00116 AC: 1286 AN: 1112000

Other (OTH) AF: 0.000580 AC: 35 AN: 60396

GnomAD4 genome AF: 0.00119 AC: 181 AN: 152248 Hom.: 1 Cov.: 33 AF XY: 0.00125 AC XY: 93 AN XY: 74442

African (AFR) AF: 0.0000481 AC: 2 AN: 41550

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00232 AC: 158 AN: 68006

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00181 Hom.: 4

Bravo AF: 0.000812

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00158

EpiControl AF: 0.00113

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.3
DANN	Benign	0.53
PhyloP100		1.7
Mutation Taster		=100/0	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: rs138784927; hg19: chr2-11798674; COSMIC: COSV60991715;