rs45596934

Variant names:

• chr9-84813704-G-A
• rs45596934
• ENST00000359847.4:c.*3125G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-84813704-G-A
• chr9-84813704-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001007097.3(NTRK2):​c.*3125G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 1,065,884 control chromosomes in the GnomAD database, including 886 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.034 (148 hom., cov: 32)
  • Exomes 𝑓: 0.038 (738 hom.)
• Consequence: NTRK2 NM_001007097.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• Publications: 6 publications found

Genes affected

NTRK2 (HGNC:8032): (neurotrophic receptor tyrosine kinase 2) This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation. Mutations in this gene have been associated with obesity and mood disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

NTRK2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 58

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• obesity, hyperphagia, and developmental delay

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007097.3. 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
	NTRK2	NM_006180.6	MANE Select	c.1397-47336G>A		intron	N/A	NP_006171.2
	NTRK2	NM_001007097.3		c.*3125G>A		3_prime_UTR	Exon 15 of 15	NP_001007098.1	Q16620-2
	NTRK2	NM_001369539.1		c.*3125G>A		3_prime_UTR	Exon 13 of 13	NP_001356468.1	Q16620-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	ENST00000359847.4	TSL:1	c.*3125G>A		3_prime_UTR	Exon 14 of 14	ENSP00000352906.3	Q16620-2
	NTRK2	ENST00000395882.6	TSL:1	c.*3125G>A		3_prime_UTR	Exon 15 of 15	ENSP00000379221.1	Q16620-2
	NTRK2	ENST00000277120.8	TSL:1 MANE Select	c.1397-47336G>A		intron	N/A	ENSP00000277120.3	Q16620-4

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5134 AN: 152026 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.00836

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0563

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0376

Gnomad OTH AF: 0.0297

GnomAD4 exome AF: 0.0382 AC: 34910 AN: 913740 Hom.: 738 Cov.: 29 AF XY: 0.0380 AC XY: 16034 AN XY: 421824

African (AFR) AF: 0.00371 AC: 73 AN: 19670

American (AMR) AF: 0.101 AC: 350 AN: 3478

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 213 AN: 10254

East Asian (EAS) AF: 0.000866 AC: 13 AN: 15014

South Asian (SAS) AF: 0.0201 AC: 345 AN: 17160

European-Finnish (FIN) AF: 0.0503 AC: 17 AN: 338

Middle Eastern (MID) AF: 0.00712 AC: 15 AN: 2108

European-Non Finnish (NFE) AF: 0.0404 AC: 32757 AN: 811688

Other (OTH) AF: 0.0331 AC: 1127 AN: 34030

GnomAD4 genome AF: 0.0338 AC: 5149 AN: 152144 Hom.: 148 Cov.: 32 AF XY: 0.0352 AC XY: 2615 AN XY: 74380

African (AFR) AF: 0.00834 AC: 346 AN: 41506

American (AMR) AF: 0.0865 AC: 1323 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3468

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5184

South Asian (SAS) AF: 0.0172 AC: 83 AN: 4820

European-Finnish (FIN) AF: 0.0563 AC: 596 AN: 10582

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0376 AC: 2557 AN: 67980

Other (OTH) AF: 0.0294 AC: 62 AN: 2110

Alfa AF: 0.0197 Hom.: 13

Bravo AF: 0.0354

Asia WGS AF: 0.0120 AC: 42 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.013
DANN	Benign	0.50
PhyloP100		-2.4
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: rs45596934; hg19: chr9-87428619;