rs45596934

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359847.4(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 ENST00000359847.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.1397-47336G>A		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.1397-47336G>A		intron_variant		1	NM_006180.6	P3

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

Gnomad4 AFR exome AF: 0.00371

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.0208

Gnomad4 EAS exome AF: 0.000866

Gnomad4 SAS exome AF: 0.0201

Gnomad4 FIN exome AF: 0.0503

Gnomad4 NFE exome AF: 0.0404

Gnomad4 OTH exome AF: 0.0331

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

Gnomad4 AFR AF: 0.00834

Gnomad4 AMR AF: 0.0865

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.0563

Gnomad4 NFE AF: 0.0376

Gnomad4 OTH AF: 0.0294

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.013
DANN	Benign	0.50

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: rs45596934; hg19: chr9-87428619; COSMIC: COSV99460433;